vitamin in immune system.docx

8/14/2019 vitamin in immune system.docx

1/26

How to boost your immune system

Excerpted fromThe Truth About Your Immun e System,a Special Health Report from HarvardHealth Publications

What can you do?

On the whole, your immune system does a remarkable job of defending you against disease-causingmicroorganisms. But sometimes it fails: A germ invades successfully and makes you sick. Is it possible tointervene in this process and make your immune system stronger? What if you improve your diet? Takecertain vitamins or herbal preparations? Make other lifestyle changes in the hope of producing a near-perfect immune response?

The idea of boosting your immunity is enticing, but the ability to do so has proved elusive for severalreasons. The immune system is precisely that a system, not a single entity. To function well, it requiresbalance and harmony. There is still much that researchers dont know about the intricacies andinterconnectedness of the immune response. For now, there are no scienti fically proven direct links

between lifestyle and enhanced immune function.

But that doesnt mean the effects of lifestyle on the immune system arent intriguing and shouldnt bestudied. Quite a number of researchers are exploring the effects of diet, exercise, age, psychologicalstress, herbal supplements, and other factors on the immune response, both in animals and in humans.Although interesting results are emerging, thus far they can only be considered preliminary. Thatsbecause researchers are still trying to understand how the immune system works and how to interpretmeasurements of immune function. The following sections summarize some of the most active areas ofresearch into these topics. In the meantime, general healthy-living strategies are a good way to startgiving your immune system the upper hand.

Immunity in action.A healthy immune system can defeat invading pathogens as shown above, wheretwo bacteria that cause gonorrhea are no match for the large phagocyte, called a neutrophil, that engulfsand kills them (see arrows).

Photos courtesy of Michael N. Starnbach, Ph.D., Harvard Medical School

Adopt healthy-living strategies
https://www.health.harvard.edu/YIhttps://www.health.harvard.edu/YIhttps://www.health.harvard.edu/YIhttps://www.health.harvard.edu/YI


2/26

Your first line of defense is to choose a healthy lifestyle. Following general good-health guidelines is thesingle best step you can take toward keeping your immune system strong and healthy. Every part of yourbody, including your immune system, functions better when protected from environmental assaults andbolstered by healthy-living strategies such as these:

Dont smoke.

Eat a diet high in fruits, vegetables, and whole grains, and low in saturated fat. Exercise regularly.

Maintain a healthy weight.

Control your blood pressure.

If you drink alcohol, drink only in moderation.

Get adequate sleep.

Take steps to avoid infection, such as washing your hands frequently and cooking meatsthoroughly.

Get regular medical screening tests for people in your age group and risk category.

Be skeptical

Many products on store shelves claim to boost or support immunity. But the concept of boosting immunityactually makes little sense scientifically. In fact, boosting the number of cells in your body immune cellsor others is not necessarily a good thing. For example, athletes who engage in blood doping pumping blood into their systems to boost their number of blood cells and enhance their performance run the risk of strokes.

Attempting to boost the cells of the immune system is especially complicated because there are so manydifferent kinds of cells in the immune system that respond to so many different microbes in so many ways.Which cells should you boost, and to what number? So far, scientists do not know the answer. What isknown is that the body is continually generating immune cells. Certainly it produces many morelymphocytes than it can possibly use. The extra cells remove themselves through a natural process of celldeath called apoptosis some before they see any action, some after the battle is won. No one knowshow many cells or what kinds of cells the immune system needs to function at its optimum level.

Scientists do know more about the low end of the scale. When the number of T cells in an HIV/AIDSpatient drops below a certain level, the patient gets sick because the immune system doesnt haveenough T cells to fight off infection. So there is a bottom number below which the immune system cantdo its job. But how many T cells is comfortably enough, and beyond that point, is more better? We dontknow.

Many researchers are trying to explore the effects of a variety of factors from foods and herbalsupplements to exercise and stress on immunity. Some take measures of certain blood componentslike lymphocytes or cytokines. But thus far, no one really knows what these measurements mean in termsof your bodys ability to fight disease. They provide a way of detecting whether something is going on, butscience isnt yet sufficiently advanced to understand how this translates into success in warding offdisease.

A different scientific approach looks at the effect of certain lifestyle modifications on the incidence ofdisease. If a study shows significantly less disease, researchers consider whether the immune system isbeing strengthened in some way. Based on these studies, there is now evidence that even though wemay not be able to prove a direct link between a certain lifestyle and an improved immune response, wecan at least show that some links are likely.

Age and immunity


3/26

Earlier in this report (see Cancer: Missed cues), we noted that one active area of research is how theimmune system functions as the body ages. Researchers believe that the aging process somehow leadsto a reduction of immune response capability, which in turn contributes to more infections, moreinflammatory diseases, and more cancer. As life expectancy in developed countries has increased, so toohas the incidence of age-related conditions. Happily, investigation into the aging process can benefit usall no matter what our age.

While some people age healthily, the conclusion of many studies is that, compared with younger people,the elderly are far more likely to contract infectious diseases. Respiratory infections, influenza, andparticularly pneumonia are a leading cause of death in people over 65 worldwide. No one knows for surewhy this happens, but some scientists observe that this increased risk correlates with a decrease in Tcells, possibly from the thymus atrophying with age and producing fewer T cells to fight off infection.Thymus function declines beginning at age 1; whether this decrease in thymus function explains the dropin T cells or whether other changes play a role is not fully understood. Others are interested in whetherthe bone marrow becomes less efficient at producing the stem cells that give rise to the cells of theimmune system.

Researchers at the University of Arkansas are looking at another aspect of why the immune systemseems to weaken with age. They studied cell death in mice. They conducted an experiment to compare

the lifespan of memory T lymphocytes in older mice with those of younger mice and found that thelymphocytes in older mice die sooner. This suggests that as the lymphocytes die off, the elderly immunesystem loses its memory for the microbes it is intended to fight and fails to recognize the microbes whenthey reappear. The body thus becomes less able to mount a vigorous immune response.

A reduction in immune response to infections has been demonstrated by older peoples response tovaccines. For example, studies of influenza vaccines have shown that for people over age 65, vaccineeffectiveness was 23%, whereas for healthy children (over age 2), it was 38%. But despite the reductionin efficacy, vaccinations for influenza and S. pneumoniaehave significantly lowered the rates of sicknessand death in older people when compared with nonvaccination.

Yet other researchers are looking at the connection between nutrition and immunity in the elderly. A formof malnutrition that is surprisingly common even in affluent countries is known as micronutrient

malnutrition. Micronutrient malnutrition, in which a person is deficient in some essential vitamins andtrace minerals that are obtained from or supplemented by diet, can be common in the elderly. Olderpeople tend to eat less and often have less variety in their diets. One important question is whetherdietary supplements may help older people maintain a healthier immune system. Older people shoulddiscuss this question with a physician who is well versed in geriatric nutrition, because while some dietarysupplementation may be beneficial for older people, even small changes can have serious repercussionsin this age group.

What about diet?

Like any fighting force, the immune system army marches on its stomach. Immune system warriors needgood, regular nourishment. Scientists have long recognized that people who live in poverty and aremalnourished are more vulnerable to infectious diseases. Whether the increased rate of disease is

caused by malnutritions effect on the immune system, however, is not certain. There are still relativelyfew studies of the effects of nutrition on the immune system of humans, and even fewer studies that tiethe effects of nutrition directly to the development (versus the treatment) of diseases.

There are studies of the effects of nutritional changes on the immune systems of animals, but again thereare few studies that address the development of diseases in animals as a result of changes in immunity.For example, one group of investigators has found that in mice, diets deficient in protein reduce both thenumbers and function of T cells and macrophages and also reduce the production of immunoglobulin A(IgA) antibody.


4/26

There is some evidence that various micronutrient deficiencies for example, deficiencies of zinc,selenium, iron, copper, folic acid, and vitamins A, B6, C, and E alter immune responses in animals, asmeasured in the test tube. However, the impact of these immune system changes on the health ofanimals is less clear, and the effect of similar deficiencies on the human immune response has yet to beassessed. But the research at this stage is promising, at least for some of the micronutrients.

So what can you do? If you suspect your diet is not providing you with all your micronutrient needs maybe you dont like vegetables or you choose white bread over whole grains taking a dailymultivitamin and mineral supplement brings health benefits of many types, beyond any possibly beneficialeffects on the immune system. Taking megadoses of a single vitamin does not. More is not necessarilybetter. Researchers are investigating the immune boosting potential of a number of different nutrients.

Selenium.Some studies have suggested that people with low selenium levels are at greater risk ofbladder, breast, colon, rectum, lung, and prostate cancers. A large-scale, multiyear study is currently inprogress to look at the effects of combining selenium and vitamin E on prostate cancer prevention.

Vitamin A.Experts have long known that vitamin A plays a role in infection and maintaining mucosalsurfaces by influencing certain subcategories of T cells and B cells and cytokines. Vitamin A deficiency isassociated with impaired immunity and increased risk of infectious disease. On the other hand, according

to one study, supplementation in the absence of a deficiency didnt enhance or suppress T cell immunityin a group of healthy seniors.

Vitamin B2.There is some evidence that vitamin B2 enhances resistance to bacterial infections in mice,but what that means in terms of enhancing immune response is unclear.

Vitamin B6.Several studies have suggested that a vitamin B6 deficiency can depress aspects of theimmune response, such as lymphocytes ability to mature and spin off into various types of T and B cells.Supplementing with moderate doses to address the deficiency restores immune function, but megadosesdont produce additional benefits. And B6 may promote the growth of tumors.

Vitamin C.The jury is still out on vitamin C and the immune system. Many studies have looked at vitaminC in general; unfortunately, many of them were not well designed. Vitamin C may work in concert with

other micronutrients rather than providing benefits alone.

Vitamin D.For many years doctors have known that people afflicted with tuberculosis responded well tosunlight. An explanation may now be at hand. Researchers have found that vitamin D, which is producedby the skin when exposed to sunlight, signals an antimicrobial response to the bacterium responsible fortuberculosis, Mycobacterium tuberculosis. Whether vitamin D has similar ability to fight off other diseasesand whether taking vitamin D in supplement form is beneficial are questions that need to be resolved withfurther study.

Vitamin E.A study involving healthy subjects over age 65 has shown that increasing the daily dose ofvitamin E from the recommended dietary allowance (RDA) of 30 mg to 200 mg increased antibodyresponses to hepatitis B and tetanus after vaccination. But these increased responses didnt happenfollowing administration of diphtheria and pneumococcal vaccines.

Zinc.Zinc is a trace element essential for cells of the immune system, and zinc deficiency affects theability of T cells and other immune cells to function as they should. Caution: While its important to havesufficient zinc in your diet (1525 mg per day), too much zinc can inhibit the function of the immunesystem.

Herbs and other supplements


5/26

Walk into a store, and you will find bottles of pills and herbal preparations that claim to support immunityor otherwise boost the health of your immune system. Although some preparations have been found toalter some components of immune function, thus far there is no evidence that they actually bolsterimmunity to the point where you are better protected against infection and disease. Demonstratingwhether an herb or any substance, for that matter can enhance immunity is, as yet, a highlycomplicated matter. Scientists dont know, for example, whether an herb that seems to raise the levels ofantibodies in the blood is actually doing anything beneficial for overall immunity.

But that doesnt mean we should discount the benefits of all herbal preparations. Everyones immunesystem is unique. Each persons physiology responds to active substances differently. So if y ourgrandmother says shes been using an herbal preparation for years that protects her from illness, whosto say that it doesnt? The problem arises when scientists try to study such a preparation among largenumbers of people. The fact that it works for one person wont show up in the research data if its notdoing the same for a larger group.

Scientists have looked at a number of herbs and vitamins in terms of their potential to influence theimmune system in some way. Much of this research has focused on the elderly, children, or people withcompromised immune systems, such as AIDS patients. And many of the studies have had design flaws,which means further studies are needed to confirm or disprove the results. Consequently, these findings

should not be considered universally applicable.

Some of the supplements that have drawn attention from researchers are these:

Aloe vera.For now, theres no evidence that aloe vera can modulate immune response. Because manydifferent formulations and compounds have been used in studies, comparing the results is difficult.However, there is some evidence that topical aloe vera is helpful for minor burns, wounds, or frostbite,and also for skin inflammations when combined with hydrocortisone. Studies have found aloe vera is notthe best option for treating breast tissue after radiation therapy.

Astragalus membranes.The astragalus product, which is derived from the root of the plant, is marketedas an immune-system stimulant, but the quality of the studies demonstrating the immune-stimulatingproperties of astragalus are poor. Furthermore, it may be dangerous.

Echinacea.An ocean of ink has been spilled extolling echinacea as an immune stimulant, usually interms of its purported ability to prevent or limit the severity of colds. Most experts dont recommend takingechinacea on a long-term basis to prevent colds. A group of physicians from Harvard Medical Schoolnotes that studies looking at the cold prevention capabilities of echinacea have not been well designed,and other claims regarding echinacea are as yet not proven. Echinacea can also cause potentiallyserious side effects. People with ragweed allergies are more likely to have a reaction to echinacea, andthere have been cases of anaphylactic shock. Injected echinacea in particular has caused severereactions. A well-designed study by pediatricians at the University of Washington in Seattle foundechinacea didnt help with the duration and severity of cold symptoms in a group of children. A large 2005study of 437 volunteers also found that echinacea didnt affect the rate of cold infections or the progressand severity of a cold.

Garlic.Garlic may have some infection-fighting capability. In laboratory tests, researchers have seengarlic work against bacteria, viruses, and fungi. Although this is promising, there havent been enoughwell-designed human studies conducted to know whether this translates into human benefits. One 2006study that looked at rates for certain cancers and garlic and onion consumption in southern Europeanpopulations found an association between the frequency of use of garlic and onions and a lower risk ofsome common cancers. Until more is known, however, its too early to recommend garlic as a way oftreating or preventing infections or controlling cancer.


6/26

Ginseng.Its not clear how the root of the ginseng plant works, but claims on behalf of Asian ginseng aremany, including its ability to stimulate immune function. Despite the claims of a number of mainly smallstudies, the National Center for Complementary and Alternative Medicine (NCCAM) considers there havebeen insufficient large studies of a high enough quality to support the claims. NCCAM is currentlysupporting research to understand Asian ginseng more fully.

Glycyrrhiza glabra (licorice root).Licorice root is used in Chinese medicine to treat a variety ofillnesses. Most studies of licorice root have been done in combination with other herbs, so its notpossible to verify whether any effects were attributable to licorice root per se. Because of the potentialside effects of taking licorice and how little is known about its benefits if any for stimulating immunefunction, this is an herb to avoid.

Probiotics.There are hundreds of different species of bacteria in your digestive tract, which do a bang-up job helping you digest your food. Now researchers, including some at Harvard Medical School, arefinding evidence of a relationship between such good bacteria and the immune system. For instance, itis now known that certain bacteria in the gut influence the development of aspects of the immune system,such as correcting deficiencies and increasing the numbers of certain T cells. Precisely how the bacteriainteract with the immune system components isnt known. As more and more intriguing evidence comesin to support the link that intestinal bacteria bolster the immune system, its tempting to think that more

good bacteria would be better. At least, this is what many marketers would like you to believe as they touttheir probiotic products.

Probiotics are good bacteria, such as Lactobacillusand Bifidobacterium,that can safely dwell in yourdigestive tract. Youll now find probioticslisted on the labels of dairy products, drinks, cereals, energybars, and other foods. Ingredients touted as prebiotics, which claim to be nutrients that feed the goodbacteria, are also cropping up in commercially marketed foods. Unfortunately, the direct connectionbetween taking these products and improving immune function has not yet been made. Nor has scienceshown whether taking probiotics will replenish the good bacteria that get knocked out together with badbacteria when you take antibiotics.

Another caution is that the quality of probiotic products is not consistent. Some contain what they say theydo; some do not. In a 2006 report, the American Academy of Microbiology said that at present, the

quality of probiotics available to consumers in food products around the world is unreliable. In the samevein, the FDA monitors food packages to make sure they dont carry labels that claim the products cancure diseases unless the companies have scientific evidence to support the claims. Does this meantaking probiotics is useless? No. It means the jury is still out on the expansive health claims. In themeantime, if you choose to take a probiotic in moderation, it probably wont hurt, and the scientificevidence may ultimately show some benefit.

The stress connection

Modern medicine, which once treated the connection between emotions and physical health withskepticism, has come to appreciate the closely linked relationship of mind and body. A wide variety ofmaladies, including stomach upset, hives, and even heart disease, are linked to the effects of emotionalstress. But although the relationship between stress and immune function is being studied by a number of

different types of scientists, so far it is not a major area of research for immunologists.

Studying the relationship between stress and the immune system presents difficult challenges. For onething, stress is difficult to define. What may appear to be a stressful situation for one person is not foranother. When people are exposed to situations they regard as stressful, it is difficult for them to measurehow much stress they feel, and difficult for the scientist to know if a persons subjective impression of theamount of stress is accurate. The scientist can only measure things that may reflect stress, such as thenumber of times the heart beats each minute, but such measures also may reflect other factors.


7/26

Most scientists studying the relationship of stress and immune function, however, do not study a sudden,short-lived stressor; rather, they try to study more constant and frequent stressors known as chronicstress, such as that caused by relationships with family, friends, and co-workers, or sustained challengesto perform well at ones work. Some scientists are investigating whether ongoing stress takes a toll on theimmune system.

But it is hard to perform what scientists call controlled experiments in human beings. In a controlledexperiment, the scientist can change one and only one factor, such as the amount of a particularchemical, and then measure the effect of that change on some other measurable phenomenon, such asthe amount of antibodies produced by a particular type of immune system cell when it is exposed to thechemical. In a living animal, and especially in a human being, that kind of control is just not possible,since there are so many other things happening to the animal or person at the time that measurementsare being taken.

Despite these inevitable difficulties in measuring the relationship of stress to immunity, scientists whorepeat the same experiment many times with many different animals or human beings, and who get thesame result most of the time, hope that they can draw reasonable conclusions.

Some researchers place animals into stressful situations, such as being trapped in a small space or being

placed near an aggressive animal. Different functions of their immune systems, and their health, are thenmeasured under such stressful conditions. On the basis of such experiments, some published studieshave made the following claims:

Experimentally created stressful situations delayed the production of antibodies in mice infectedwith influenza virus and suppressed the activity of T cells in animals inoculated with herpessimplex virus.

Social stress can be even more damaging than physical stress. For example, some mice wereput into a cage with a highly aggressive mouse two hours a day for six days and repeatedlythreatened, but not injured, by the aggressive mouse a social stress. Other mice were kept intiny cages without food and water for long periods a physical stress. Both groups of micewere exposed to a bacterial toxin, and the socially stressed animals were twice as likely to die.

Isolation can also suppress immune function. Infant monkeys separated from their mothers,

especially if they are caged alone rather than in groups, generate fewer lymphocytes in responseto antigens and fewer antibodies in response to viruses.

Many researchers report that stressful situations can reduce various aspects of the cellular immuneresponse. A research team from Ohio State University that has long worked in this field suggests thatpsychological stress affects the immune system by disrupting communication between the nervoussystem, the endocrine (hormonal) system, and the immune system. These three systems talk to oneanother using natural chemical messages, and must work in close coordination to be effective. The OhioState research team speculates that long-term stress releases a long-term trickle of stress hormones mainly glucocorticoids. These hormones affect the thymus, where lymphocytes are produced, and inhibitthe production of cytokines and interleukins, which stimulate and coordinate white blood cell activity. Thisteam and others have reported the following results:

Elderly people caring for relatives with Alzheimers disease have higher than average levels ofcortisol, a hormone secreted by the adrenal glands and, perhaps because of the higher levels ofcortisol, make fewer antibodies in response to influenza vaccine.

Some measures of T cell activity have been found to be lower in depressed patients comparedwith nondepressed patients, and in men who are separated or divorced compared with men whoare married.

In a year-long study of people car ing for husbands or wives with Alzheimers disease, changes inT cell function were greatest in those who had the fewest friends and least outside help.


8/26

Four months after the passage of Hurricane Andrew in Florida, people in the most heavilydamaged neighborhoods showed reduced activity in several immune system measurements.Similar results were found in a study of hospital employees after an earthquake in Los Angeles.

In all of these studies, however, there was no proof that the immune system changes measured had anyclear adverse effects on health in these individuals.

Does being cold make you sick?

Almost every mother has said it: Wear a jacket or youll catch a cold! Is she right? So far, researcherswho are studying this question think that normal exposure to moderate cold doesnt increase yoursusceptibility to infection. Most health experts agree that the reason winter is cold and flu season is notthat people are cold, but that they spend more time indoors, in closer contact with other people who canpass on their germs.

But researchers remain interested in this question in different populations. Some experiments with micesuggest that cold exposure might reduce the ability to cope with infection. But what about humans?Scientists have dunked people in cold water and made others sit nude in subfreezing temperatures.Theyve studied people who lived in Antarctica and those on expeditions in the Canadian Rockies. Theresults have been mixed. For example, researchers documented an increase in upper respiratoryinfections in competitive cross-country skiers who exercise vigorously in the cold, but whether theseinfections are due to the cold or other factors such as the intense exercise or the dryness of the air is not known. Theyve found that exposure to cold does increase levels of some cytokines, the proteinsand hormones that act as messengers in the immune system, but how this affects health isnt clear.

A group of Canadian researchers that has reviewed hundreds of medical studies on the subject andconducted some of its own research concludes that theres no need to worry about moderate coldexposure it has no detrimental effect on the human immune system. Should you bundle up when itscold outside? The answer is yes if youre uncomfortable, or if youre going to be outdoors for anextended period where such problems as frostbite and hypothermia are a risk. But dont worry aboutimmunity.

Exercise: Good or bad for immunity?

Regular exercise is one of the pillars of healthy living. It improves cardiovascular health, lowers bloodpressure, helps control body weight, and protects against a variety of diseases. But does it help maintaina healthy immune system? Just like a healthy diet, exercise can contribute to general good health andtherefore to a healthy immune system. It may contribute even more directly by promoting good circulation,which allows the cells and substances of the immune system to move through the body freely and dotheir job efficiently.

Some scientists are trying to take the next step to determine whether exercise directly affects a personssusceptibility to infection. For example, some researchers are looking at whether extreme amounts ofintensive exercise can cause athletes to get sick more often or somehow impairs their immune function.

To do this sort of research, exercise scientists typically ask athletes to exercise intensively; the scientiststest their blood and urine before and after the exercise to detect any changes in immune systemcomponents such as cytokines, white blood cells, and certain antibodies. While some changes have beenrecorded, immunologists do not yet know what these changes mean in terms of human immuneresponse. No one yet knows, for example, whether an increase in cytokines is helpful or has any trueeffect on immune response. Similarly, no one knows whether a general increase in white cell count is agood thing or a bad thing.


9/26

But these subjects are elite athletes undergoing intense physical exertion. What about moderate exercisefor average people? Does it help keep the immune system healthy? For now, even though a directbeneficial link hasnt been established, its reasonable to consider moderate regular exercise to be abeneficial arrow in the quiver of healthy living, a potentially important means for keeping your immunesystem healthy along with the rest of your body.

One approach that could help researchers get more complete answers about whether lifestyle factorssuch as exercise help improve immunity takes advantage of the sequencing of the human genome. Thisopportunity for research based on updated biomedical technology can be employed to give a morecomplete answer to this and similar questions about the immune system. For example, microarrays orgene chips based on the human genome allow scientists to look simultaneously at how thousands ofgene sequences are turned on or off in response to specific physiological conditions for example,blood cells from athletes before and after exercise. Researchers hope to use these tools to analyzepatterns in order to better understand how the many pathways involved act at once.

Sumber:http://www.health.harvard.edu/flu-resource-center/how-to-boost-your-immune-system.htm
http://www.health.harvard.edu/flu-resource-center/how-to-boost-your-immune-system.htmhttp://www.health.harvard.edu/flu-resource-center/how-to-boost-your-immune-system.htmhttp://www.health.harvard.edu/flu-resource-center/how-to-boost-your-immune-system.htmhttp://www.health.harvard.edu/flu-resource-center/how-to-boost-your-immune-system.htm


10/26

Vitamin D: its role and uses inimmunology1

1. HECTOR F. DELUCA2and2. MARGHERITA T. CANTORNA*

+Author Affiliations1. Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706,

USA; and

2. *Department of Nutrition, Pennsylvania State University, University Park, Pennsylvania 16802,

USA

1. Correspondence: 2Correspondence: Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Dr.,Madison, WI 53706-1544, USA. E-mail:[email protected]

Next Section

Abstract

In recent years there has been an effort to understand possible noncalcemic roles of vitamin D, including its role inthe immune system and, in particular, on T cell-medicated immunity. Vitamin D receptor is found in significant

concentrations in the T lymphocyte and macrophage populations. However, its highest concentration is in the

immature immune cells of the thymus and the mature CD-8 T lymphocytes. The significant role of vitamin D

compounds as selective immunosuppressants is illustrated by their ability to either prevent or markedly suppress

animal models of autoimmune disease. Results show that 1,25-dihydroxyvitamin D3can either prevent or markedly

suppress experimental autoimmune encephalomyelitis, rheumatoid arthritis, systemic lupus erythematosus, type I

diabetes, and inflammatory bowel disease. In almost every case, the action of the vitamin D hormone requires that

the animals be maintained on a normal or high calcium diet. Possible mechanisms of suppression of these

autoimmune disorders by the vitamin D hormone have been presented. The vitamin D hormone stimulates

transforming growth factor TGF-1 and interleukin 4 (IL-4) production, which in turn may suppress inflammatory T

cell activity. In support of this, the vitamin D hormone is unable to suppress a murine model of the human disease

multiple sclerosis in IL-4-deficient mice. The results suggest an important role for vitamin D in autoimmune

disorders and provide a fertile and interesting area of research that may yield important new therapies.DeLuca, H.

F., Cantorna, M. T. Vitamin D: its role and uses in immunology.

autoimmune diseases

vitamin D as immunomodulator

inflammatory disease

vitamin D and immunity

UNTIL 1980, NO ONEhad imagined that vitamin D might play a role in the functioning of the

immune system. The function of vitamin D was largely considered to be in the area of calcium,

phosphorus, and bone metabolism. It prevents rickets in children, osteomalacia in adults, and
http://www.fasebj.org/content/15/14/2579.full#fn-1http://www.fasebj.org/search?author1=HECTOR+F.+DELUCA&sortspec=date&submit=Submithttp://www.fasebj.org/search?author1=HECTOR+F.+DELUCA&sortspec=date&submit=Submithttp://www.fasebj.org/search?author1=HECTOR+F.+DELUCA&sortspec=date&submit=Submithttp://www.fasebj.org/search?author1=MARGHERITA+T.+CANTORNA&sortspec=date&submit=Submithttp://www.fasebj.org/search?author1=MARGHERITA+T.+CANTORNA&sortspec=date&submit=Submithttp://www.fasebj.org/search?author1=MARGHERITA+T.+CANTORNA&sortspec=date&submit=Submithttp://www.fasebj.org/content/15/14/2579.fullhttp://www.fasebj.org/content/15/14/2579.full#xref-corresp-1-1http://www.fasebj.org/content/15/14/2579.full#xref-corresp-1-1mailto:[email protected]:[email protected]:[email protected]://www.fasebj.org/content/15/14/2579.full#ack-1http://www.fasebj.org/content/15/14/2579.full#ack-1http://www.fasebj.org/search?fulltext=autoimmune+diseases&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/search?fulltext=autoimmune+diseases&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/search?fulltext=vitamin+D+as+immunomodulator&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/search?fulltext=vitamin+D+as+immunomodulator&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/search?fulltext=inflammatory+disease&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/search?fulltext=inflammatory+disease&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/search?fulltext=vitamin+D+and+immunity&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/search?fulltext=vitamin+D+and+immunity&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/search?fulltext=vitamin+D+and+immunity&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/search?fulltext=inflammatory+disease&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/search?fulltext=vitamin+D+as+immunomodulator&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/search?fulltext=autoimmune+diseases&sortspec=date&submit=Submit&andorexactfulltext=phrasehttp://www.fasebj.org/content/15/14/2579.full#ack-1mailto:[email protected]://www.fasebj.org/content/15/14/2579.full#xref-corresp-1-1http://www.fasebj.org/content/15/14/2579.fullhttp://www.fasebj.org/search?author1=MARGHERITA+T.+CANTORNA&sortspec=date&submit=Submithttp://www.fasebj.org/search?author1=MARGHERITA+T.+CANTORNA&sortspec=date&submit=Submithttp://www.fasebj.org/search?author1=HECTOR+F.+DELUCA&sortspec=date&submit=Submithttp://www.fasebj.org/search?author1=HECTOR+F.+DELUCA&sortspec=date&submit=Submithttp://www.fasebj.org/content/15/14/2579.full#fn-1


11/26

hypocalcemic tetany. The major thrust of research until 1980 was to determine how vitamin D

functions in these important processes of mineral metabolism regulation.

In 1968, the idea appeared that vitamin D itself is biologically inactive and must be

metabolically activated before it can function (1,2).This led to the isolation and chemical

identification of the active forms of vitamin D in 19681971 (3).Continued pursuit of the

metabolism of vitamin D resulted in the understanding that vitamin D must first be

hydroxylated in the liver to form 25-hydroxyvitamin D3(25-OH-D3), the major circulating form

of the vitamin. This form of vitamin D was subsequently found to be metabolically inactive and

must be further converted to a final active form, 1,25-dihydroxyvitamin D3(1,25-(OH)2D3) (3,

4).This last step occurs predominantly if not exclusively in the proximal convoluted tubule

cells of the kidney to produce the metabolically active form of vitamin D, 1,25-(OH)2D3. This

major calcium mobilizing hormone then functions directly on the enterocyte of the small

intestine to markedly increase the absorption of calcium and phosphorus from the lumen into

the plasma compartment. It also plays a major role in the mobilization of calcium from bone

when parathyroid hormone is present. Together with parathyroid hormone, it markedly

improves the renal reabsorption of calcium in the distal tubule (3,4).These actions result in

the elevation of plasma calcium and phosphorus levels to supersaturating conditions that are

necessary to support mineralization of the skeleton on the one hand and prevent hypocalcemic

tetany on the other (3,4).The production of the vitamin D hormone is regulated by the need

for calcium and phosphorus (456).Slightly low levels of plasma calcium will stimulate the

parathyroids to produce and secrete the parathyroid hormone. This hormone binds to

osteoblasts of bone and the entire length of the nephron of the kidney (345).In the kidney,

parathyroid hormone stimulates the 1-hydroxylase enzyme that produces the final vitamin D

hormone. If calcium in plasma rises to very high levels, calcitonin is secreted from the c cells of

the thyroid gland. This peptide hormone binds to the osteoblasts and osteoclasts to prevent the

mobilization of calcium from bone; thus causing a reduction in plasma calcium levels. The

exact details of this elegant endocrine system are reported elsewhere (12345)

The attempt to understand how the active form of vitamin D carries out its functions led to the

discovery of the vitamin D receptor (VDR) in 1974 and 1975 (6,7).Before this, however,

synthesis of radiolabeled 1,25-(OH)2D3of high specific activity allowed for frozen section

autoradiography of physiological doses of this hormone. It became clear that this hormone

localized almost entirely in the nucleus in a specific fashion in target tissues. This localization

was also found in other tissues not previously considered targets (8,9).For example,

keratinocytes of skin, islet cells of the pancreas, lymphocytes, and promyelocytes showed

specific nuclear localization of 1,25-(OH)2D3and the presence of the VDR. The discovery of the

VDR in these tissues resulted in the idea that the vitamin D hormone had functions beyond

calcium and phosphorus metabolism, which prompted investigations into the noncalcemic

actions of the vitamin D hormone (10).Perhaps the most important was the discovery of the

VDR in the parathyroid glands (9,11,12)and the demonstration that the vitamin D

hormone functions through its receptor to suppress the preproparathyroid gene (13)and

parathyroid cell proliferation (14).This, then, is the basis of the treatment of secondary
http://www.fasebj.org/content/15/14/2579.full#ref-1http://www.fasebj.org/content/15/14/2579.full#ref-1http://www.fasebj.org/content/15/14/2579.full#ref-2http://www.fasebj.org/content/15/14/2579.full#ref-2http://www.fasebj.org/content/15/14/2579.full#ref-2http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-5http://www.fasebj.org/content/15/14/2579.full#ref-5http://www.fasebj.org/content/15/14/2579.full#ref-6http://www.fasebj.org/content/15/14/2579.full#ref-6http://www.fasebj.org/content/15/14/2579.full#ref-6http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-5http://www.fasebj.org/content/15/14/2579.full#ref-5http://www.fasebj.org/content/15/14/2579.full#ref-5http://www.fasebj.org/content/15/14/2579.full#ref-1http://www.fasebj.org/content/15/14/2579.full#ref-2http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-5http://www.fasebj.org/content/15/14/2579.full#ref-5http://www.fasebj.org/content/15/14/2579.full#ref-5http://www.fasebj.org/content/15/14/2579.full#ref-6http://www.fasebj.org/content/15/14/2579.full#ref-6http://www.fasebj.org/content/15/14/2579.full#ref-7http://www.fasebj.org/content/15/14/2579.full#ref-7http://www.fasebj.org/content/15/14/2579.full#ref-7http://www.fasebj.org/content/15/14/2579.full#ref-8http://www.fasebj.org/content/15/14/2579.full#ref-8http://www.fasebj.org/content/15/14/2579.full#ref-9http://www.fasebj.org/content/15/14/2579.full#ref-9http://www.fasebj.org/content/15/14/2579.full#ref-9http://www.fasebj.org/content/15/14/2579.full#ref-10http://www.fasebj.org/content/15/14/2579.full#ref-10http://www.fasebj.org/content/15/14/2579.full#ref-10http://www.fasebj.org/content/15/14/2579.full#ref-9http://www.fasebj.org/content/15/14/2579.full#ref-9http://www.fasebj.org/content/15/14/2579.full#ref-11http://www.fasebj.org/content/15/14/2579.full#ref-11http://www.fasebj.org/content/15/14/2579.full#ref-12http://www.fasebj.org/content/15/14/2579.full#ref-12http://www.fasebj.org/content/15/14/2579.full#ref-12http://www.fasebj.org/content/15/14/2579.full#ref-13http://www.fasebj.org/content/15/14/2579.full#ref-13http://www.fasebj.org/content/15/14/2579.full#ref-13http://www.fasebj.org/content/15/14/2579.full#ref-14http://www.fasebj.org/content/15/14/2579.full#ref-14http://www.fasebj.org/content/15/14/2579.full#ref-14http://www.fasebj.org/content/15/14/2579.full#ref-14http://www.fasebj.org/content/15/14/2579.full#ref-13http://www.fasebj.org/content/15/14/2579.full#ref-12http://www.fasebj.org/content/15/14/2579.full#ref-11http://www.fasebj.org/content/15/14/2579.full#ref-9http://www.fasebj.org/content/15/14/2579.full#ref-10http://www.fasebj.org/content/15/14/2579.full#ref-9http://www.fasebj.org/content/15/14/2579.full#ref-8http://www.fasebj.org/content/15/14/2579.full#ref-7http://www.fasebj.org/content/15/14/2579.full#ref-6http://www.fasebj.org/content/15/14/2579.full#ref-5http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-2http://www.fasebj.org/content/15/14/2579.full#ref-1http://www.fasebj.org/content/15/14/2579.full#ref-5http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-6http://www.fasebj.org/content/15/14/2579.full#ref-5http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-4http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-3http://www.fasebj.org/content/15/14/2579.full#ref-2http://www.fasebj.org/content/15/14/2579.full#ref-1


12/26

hyperparathyroidism found in the dialysis patients and constitutes a major therapeutic

application of 1,25-(OH)2D3and its analogs.

Noting VDR in promyelocytes, Abe et al. and Tanaka et al. demonstrated that the vitamin D

hormone can suppress proliferation of promyelocytes and cause their differentiation into the

monocyte (15,16).Similar effects of the vitamin D hormone on several cancerous cell lines

ensued (17).A role for the vitamin D hormone in cellular differentiation thus became known.

These findings prompted a search to use vitamin D analogs to treat cancer and underscored the

idea that the vitamin D hormone has functions beyond calcium, phosphorus, and bone. Table

1provides a list of possible target cells of the vitamin D hormone including the classical sites

of intestine, kidney, and bone.

The work of Manolagas and his group provided the first strong evidence that activated

lymphocytes contain significant quantities of the VDR (181920).Numerous in vitro studies

followed in which the vitamin D hormone could be shown to increase proliferation or suppress

proliferation, depending on the experiment and how it was conducted (21).It is undeniable

that peripheral lymphocytes, macrophages, and thymus tissue contain the VDR. In fact, calf

thymus proved to be an excellent source of the VDR to be used for competitive binding assays

in the measurement of the vitamin D hormone (22).These findings then raised the question of

what effect vitamin D might have on the immune system.

In our own laboratory we determined which cells of the lymphocyte population contain the

largest amounts of the VDR (21).By purifying lymphocytes to homogeneity, we were able to

demonstrate that the CD-8 lymphocytes have the highest concentrations of the VDR, whether

or not they were activated. Most important, the presence of 1,25-(OH)2D3increases the amount

of measurable receptor, probably because it improves the longevity and stability of the receptor

in vivo as well as in vitro (23).The CD4 lymphocytes and macrophages contain relatively small

but significant amounts of the VDR. Figure 1illustrates the VDR levels in cells of the immune

system.

The next important advance in the role of vitamin D in the immune system came from studies

of vitamin D-deficient mice (24).Making mice vitamin D deficient proved not to be a trivial

matter, and two generations of mice reproducing under low vitamin D conditions were required.

Having accomplished this, S. Yang in my group demonstrated that delayed hypersensitivity

response to dinitrobenzene is impaired under conditions of vitamin D deficiency (24).This

same response was also suppressed with supplemental 1,25-(OH)2D3(25).It became evident,

therefore, that T cell-mediated immunity is under modulatory control of 1,25-(OH)2D3. In its

absence, T cell-mediated immune responses were blunted; with high doses of the vitamin D

hormone, the same response could also be blunted. Similar immunosuppression was reported

with interesting analogs of the vitamin D hormone including 22-oxa-1,25-(OH)2D3(26)and

the 16-ene-23-yne-1,25-(OH)2D (27).These vitamin D compounds began to be known as

immunosuppressants.

Based on the reported immunosuppressant activities of the vitamin D hormone, we decided to

test the idea that certain autoimmune diseases involving hyperactive T cell-mediated immunity

might be suitable for further study (28).We focused on the disease, experimental autoimmune

encephalomyelitis (EAE) in mice. We selected B10.PL mice as the model because the sequence of
http://www.fasebj.org/content/15/14/2579.full#ref-15http://www.fasebj.org/content/15/14/2579.full#ref-15http://www.fasebj.org/content/15/14/2579.full#ref-16http://www.fasebj.org/content/15/14/2579.full#ref-16http://www.fasebj.org/content/15/14/2579.full#ref-16http://www.fasebj.org/content/15/14/2579.full#ref-17http://www.fasebj.org/content/15/14/2579.full#ref-17http://www.fasebj.org/content/15/14/2579.full#ref-17http://www.fasebj.org/content/15/14/2579.full#T1http://www.fasebj.org/content/15/14/2579.full#T1http://www.fasebj.org/content/15/14/2579.full#ref-18http://www.fasebj.org/content/15/14/2579.full#ref-19http://www.fasebj.org/content/15/14/2579.full#ref-20http://www.fasebj.org/content/15/14/2579.full#ref-20http://www.fasebj.org/content/15/14/2579.full#ref-20http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-22http://www.fasebj.org/content/15/14/2579.full#ref-22http://www.fasebj.org/content/15/14/2579.full#ref-22http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-23http://www.fasebj.org/content/15/14/2579.full#ref-23http://www.fasebj.org/content/15/14/2579.full#ref-23http://www.fasebj.org/content/15/14/2579.full#F1http://www.fasebj.org/content/15/14/2579.full#F1http://www.fasebj.org/content/15/14/2579.full#ref-24http://www.fasebj.org/content/15/14/2579.full#ref-24http://www.fasebj.org/content/15/14/2579.full#ref-24http://www.fasebj.org/content/15/14/2579.full#ref-24http://www.fasebj.org/content/15/14/2579.full#ref-24http://www.fasebj.org/content/15/14/2579.full#ref-24http://www.fasebj.org/content/15/14/2579.full#ref-25http://www.fasebj.org/content/15/14/2579.full#ref-25http://www.fasebj.org/content/15/14/2579.full#ref-25http://www.fasebj.org/content/15/14/2579.full#ref-26http://www.fasebj.org/content/15/14/2579.full#ref-26http://www.fasebj.org/content/15/14/2579.full#ref-26http://www.fasebj.org/content/15/14/2579.full#ref-27http://www.fasebj.org/content/15/14/2579.full#ref-27http://www.fasebj.org/content/15/14/2579.full#ref-27http://www.fasebj.org/content/15/14/2579.full#ref-28http://www.fasebj.org/content/15/14/2579.full#ref-28http://www.fasebj.org/content/15/14/2579.full#ref-28http://www.fasebj.org/content/15/14/2579.full#ref-28http://www.fasebj.org/content/15/14/2579.full#ref-27http://www.fasebj.org/content/15/14/2579.full#ref-26http://www.fasebj.org/content/15/14/2579.full#ref-25http://www.fasebj.org/content/15/14/2579.full#ref-24http://www.fasebj.org/content/15/14/2579.full#ref-24http://www.fasebj.org/content/15/14/2579.full#F1http://www.fasebj.org/content/15/14/2579.full#ref-23http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-22http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-20http://www.fasebj.org/content/15/14/2579.full#ref-19http://www.fasebj.org/content/15/14/2579.full#ref-18http://www.fasebj.org/content/15/14/2579.full#T1http://www.fasebj.org/content/15/14/2579.full#ref-17http://www.fasebj.org/content/15/14/2579.full#ref-16http://www.fasebj.org/content/15/14/2579.full#ref-15


13/26

neural degenerative symptoms that result in these mice after myelin basic protein injection is

similar to human multiple sclerosis (MS). We succeeded in establishing EAE and showed there

was an incidence of 100% in B10.PL mice fed a 0.87% calcium diet containing dietary vitamin D.

However, the provision of 1,25-(OH)2D3at 50200 ng/day could prevent the appearance of the

EAE lesions. If the vitamin D compound was given postimmunization, it prevented further

development of the disease (28).By now we have carried out extensive experiments on this

experimental model of autoimmune disease and have found that the vitamin D compounds

(including some important potent analogs) are extremely effective in blocking the development

of EAE.

In our attempt to reduce the hypercalcemic effects of 1,25-(OH)2D3, we provided this compound

to animals maintained on a very low calcium diet (29).To our surprise, the low calcium diet

produced a lower incidence of disease that was resistant to treatment with the vitamin D

hormone (29)(see Fig. 2). On the other hand, when similar examinations were followed in the

high calcium diet, the vitamin D compounds were effective (Fig. 3). Thus, it became clear that

calcium is required for the vitamin D suppression of the autoimmune disease, EAE. Our initial

clinical trial with the analog 19-nor-1,25-(OH)2D2(30)revealed little effectiveness in

preventing new MS lesions primarily because we failed to simultaneously provide a normal to

high calcium intake. The results, therefore, imply that a high calcium diet is required for the

vitamin D hormone to be effective in the treatment of EAE.

The success with EAE suggested that vitamin D compounds could be used to treat other

autoimmune disorders. Rheumatoid arthritis proved to be another example of an autoimmune

disorder that can be largely prevented by the administration of the 1-hydroxylated vitamin D

compounds, including 1,25-(OH)2D3(31).Two autoimmune models of rheumatoid arthritis

were used. One is the disorder caused by Lymes disease or the organismBorrelia burgdorferi; the

other is collagen-induced arthritis. An example of collagen-induced arthritis and its prevention

by the administration of 1,25-(OH)2D3is illustrated in Fig. 4. Although little more was done in

studying this disorder, high calcium intakes were not required for vitamin D compounds to

prevent the lesions.

Another example not yet reported in the literature from our group is systemic lupus

erythematosus (SLE). In 1992, Lemire et al. described an attenuation of this disorder by 1,25-

(OH)2D3injected three times a week to MRL mice (32).However, they were unable to attenuate

the rising proteinuria characteristic of this disorder and reduced the dietary calcium level in the

group of mice receiving 1,25-(OH)2D3. Therefore, it is unclear whether the low calcium diet, the

1,25-(OH)2D3, or both caused the minimal improvement reported. In our research group, MRL

mice were placed on either a 0.87% calcium, 0.3% phosphorus diet or a 0.02% calcium, 0.3%

phosphorus-purified diet. As shown in Fig. 5, nearly 75% of the MRL mice developed

proteinuria by 17 wk on the 0.87% calcium, 0.3% phosphorus diet; 50 ng/day of 1,25-

(OH)2D3incorporated into the diet prevented the proteinuria. As shown in Fig. 5, the severity

of the MRL symptoms was also markedly prevented by the administration of 1,25-(OH)2D3. In

the 0.02% calcium diet, however, the animals receiving 1,25-(OH)2D3developed SLE symptoms

earlier and appeared to be more severely affected than animals on the 0.02% calcium diet alone

(Fig. 6). Again, the results illustrate that a high calcium background is required for the vitamin
http://www.fasebj.org/content/15/14/2579.full#ref-28http://www.fasebj.org/content/15/14/2579.full#ref-28http://www.fasebj.org/content/15/14/2579.full#ref-28http://www.fasebj.org/content/15/14/2579.full#ref-29http://www.fasebj.org/content/15/14/2579.full#ref-29http://www.fasebj.org/content/15/14/2579.full#ref-29http://www.fasebj.org/content/15/14/2579.full#ref-29http://www.fasebj.org/content/15/14/2579.full#ref-29http://www.fasebj.org/content/15/14/2579.full#ref-29http://www.fasebj.org/content/15/14/2579.full#F2http://www.fasebj.org/content/15/14/2579.full#F2http://www.fasebj.org/content/15/14/2579.full#F3http://www.fasebj.org/content/15/14/2579.full#F3http://www.fasebj.org/content/15/14/2579.full#ref-30http://www.fasebj.org/content/15/14/2579.full#ref-30http://www.fasebj.org/content/15/14/2579.full#ref-30http://www.fasebj.org/content/15/14/2579.full#ref-31http://www.fasebj.org/content/15/14/2579.full#ref-31http://www.fasebj.org/content/15/14/2579.full#ref-31http://www.fasebj.org/content/15/14/2579.full#F4http://www.fasebj.org/content/15/14/2579.full#F4http://www.fasebj.org/content/15/14/2579.full#F4http://www.fasebj.org/content/15/14/2579.full#ref-32http://www.fasebj.org/content/15/14/2579.full#ref-32http://www.fasebj.org/content/15/14/2579.full#ref-32http://www.fasebj.org/content/15/14/2579.full#F5http://www.fasebj.org/content/15/14/2579.full#F5http://www.fasebj.org/content/15/14/2579.full#F5http://www.fasebj.org/content/15/14/2579.full#F5http://www.fasebj.org/content/15/14/2579.full#F6http://www.fasebj.org/content/15/14/2579.full#F6http://www.fasebj.org/content/15/14/2579.full#F6http://www.fasebj.org/content/15/14/2579.full#F6http://www.fasebj.org/content/15/14/2579.full#F5http://www.fasebj.org/content/15/14/2579.full#F5http://www.fasebj.org/content/15/14/2579.full#ref-32http://www.fasebj.org/content/15/14/2579.full#F4http://www.fasebj.org/content/15/14/2579.full#ref-31http://www.fasebj.org/content/15/14/2579.full#ref-30http://www.fasebj.org/content/15/14/2579.full#F3http://www.fasebj.org/content/15/14/2579.full#F2http://www.fasebj.org/content/15/14/2579.full#ref-29http://www.fasebj.org/content/15/14/2579.full#ref-29http://www.fasebj.org/content/15/14/2579.full#ref-28


14/26

D hormone to prevent the development of this autoimmune disorder in the MRL mice. This,

then, agrees with the results obtained with EAE.

The laboratory of Margherita Cantorna has investigated the possible treatment or prevention of

inflammatory bowel disease (IBD) by vitamin D (33).Vitamin D deficiency accelerated the

appearance of symptoms and increased the severity of IBD in interleukin 10 (IL-10) knockout

(KO) mice. Vitamin D-deficient IL-10 knockout mice developed symptoms of IBD within 68 wk

(Fig. 7). This was essentially prevented by the administration of 1,25-(OH)2D3, again under

conditions of high calcium intakes.

In our own laboratory, we have investigated the development of type I diabetes in the nonobese

diabetic (NOD) mouse model (34).These experiments were performed with animals on a 0.87%

calcium, 0.3% phosphorus diet. Vitamin D deficiency markedly accelerated the appearance and

increased the incidence of type I diabetes in the NOD mice (Fig. 8). Administration of ordinary

vitamin D partially protected the mice from developing diabetes but the rate of incidence was

still on the order of 3040%. Addition to the diet of 1,25-(OH)2D3at 50 ng/day for females and

200 ng/day for males prevented the appearance of the diabetic lesions. Mathieu et al. also

studied the appearance of diabetes in NOD mice and have reported some partial benefit by the

injection of 1,25-(OH)2D3three times a week together with a low calcium diet (35).It is not

clear whether the improvement was due to the vitamin D or due to the low calcium diet from

these studies. Furthermore, the protection appeared minimal. Another major difference was

that we incorporated 1,25-(OH)2D3into the diet at all meals vs. three times a week. With a half-

life of between 2 and 4 h in animals, it seems unlikely that i.p. dosing three times/wk is

sufficient. In any case, the autoimmune disorder in the NOD mice can be prevented by the

administration of 1,25-(OH)2D3if animals are receiving a normal to high calcium diet.

Hypercalcemia continues to be a problem and so there is an ongoing search for a true in vivo

noncalcemic analog that is still able to prevent the autoimmune disorders. So far, this has not

been successful but we are only now beginning to try to prepare true noncalcemic analogs that

are effective in vivo. It is possible that the calcemic action of 1,25-(OH)2D3is also required for

treatment of these autoimmune disorders.

Another important development has been the use of vitamin D compounds to suppress or

prevent transplant rejection (36,37).The work of Lemire et al. with a low calcium diet and

1,25-(OH)2D3three times a week showed some improvement in maintaining transplanted

organs (38).We have used the ear/heart transplant model to look at the effects of vitamin D

compounds on transplant rejection. The donor mice differed from the recipient mice by two

major histocompatability complex differences (allografts). After transplantation, the heart tissue

in this model begins to beat at 7 days. In the isografts, no rejection took place in any of the

animals; within 27 days, allograft rejection was complete. Cyclosporin A at relatively low doses

appeared not to protect whereas 1,25-(OH)2D3at 50 ng/day in the diet (again, along with 0.87%

calcium) protected the animal for as long as 100 days. Vitamin D compounds may be useful in

preventing transplant rejection.

The sum of these findings in whole animals clearly illustrates that T cell-mediated immunity

can be regulated by exogenous administration of 1-hydroxylated vitamin D compounds. The
http://www.fasebj.org/content/15/14/2579.full#ref-33http://www.fasebj.org/content/15/14/2579.full#ref-33http://www.fasebj.org/content/15/14/2579.full#ref-33http://www.fasebj.org/content/15/14/2579.full#F7http://www.fasebj.org/content/15/14/2579.full#F7http://www.fasebj.org/content/15/14/2579.full#F7http://www.fasebj.org/content/15/14/2579.full#ref-34http://www.fasebj.org/content/15/14/2579.full#ref-34http://www.fasebj.org/content/15/14/2579.full#ref-34http://www.fasebj.org/content/15/14/2579.full#F8http://www.fasebj.org/content/15/14/2579.full#F8http://www.fasebj.org/content/15/14/2579.full#ref-35http://www.fasebj.org/content/15/14/2579.full#ref-35http://www.fasebj.org/content/15/14/2579.full#ref-35http://www.fasebj.org/content/15/14/2579.full#ref-36http://www.fasebj.org/content/15/14/2579.full#ref-36http://www.fasebj.org/content/15/14/2579.full#ref-37http://www.fasebj.org/content/15/14/2579.full#ref-37http://www.fasebj.org/content/15/14/2579.full#ref-37http://www.fasebj.org/content/15/14/2579.full#ref-38http://www.fasebj.org/content/15/14/2579.full#ref-38http://www.fasebj.org/content/15/14/2579.full#ref-38http://www.fasebj.org/content/15/14/2579.full#ref-38http://www.fasebj.org/content/15/14/2579.full#ref-37http://www.fasebj.org/content/15/14/2579.full#ref-36http://www.fasebj.org/content/15/14/2579.full#ref-35http://www.fasebj.org/content/15/14/2579.full#F8http://www.fasebj.org/content/15/14/2579.full#ref-34http://www.fasebj.org/content/15/14/2579.full#F7http://www.fasebj.org/content/15/14/2579.full#ref-33


15/26

absence of vitamin D from the diet might also increase the incidence and severity of

autoimmune diseases, pointing to important regulatory actions of the vitamin D hormone.

The action of 1,25-(OH)2D3as an immunosuppressant appears to be specific since it does not

appear to interfere with the ability of the animal to act defensively against opportunist infection

(37).We have tested whether vitamin D treatment of mice makes them more susceptible totwo infectious diseases. One was an infection caused by the fungal pathogen Candida albicans, a

common infection found in transplant patients; the other was susceptibility to a viral herpes

infection. In both cases, no interference by the vitamin D compounds was found in the disease

course brought about by these organisms, whereas identical vitamin D doses were fully

effective in preventing transplant rejection. It is also important to realize that vitamin D does

not appear to act on the B lymphocyte, primarily because the B lymphocyte does not contain

VDR in appreciable amounts (21).

There have been numerous studies of in vitro behavior of a variety of T cells and macrophages,

all actors in the immune system. Although these have been contradictory and difficult to

interpret, we are beginning to see some progress in understanding the mechanism whereby

vitamin D acts as an immunosuppressant in vivo. We have measured the mRNAs encoding

cytokines in the lymphocytes found in the lymph nodes of control mice and those treated with

1,25-(OH)2D3(39).As illustrated in Fig. 9and Fig. 10, vitamin D administration markedly

increases TGF-1 and IL-4 transcripts whereas there is a reduction, if anything, in interferon

and tumor necrosis factor gene expression. These results do not differentiate between the

direct effects of vitamin D on cytokine gene expression and the indirect effects of vitamin D as

regulators of other cells and genes that result in a net change in cytokine expression. With the

availability of the IL-4 KO mice, we bred IL-4 KO mice onto the EAE susceptible B10.PL

background. In the absence of IL-4, EAE was more severe. IL-4 KO mice with EAE are also

resistant to treatment with 1,25-(OH)2D3(40).Clearly, we are just beginning to probe the

mechanisms whereby vitamin D hormone and its analogs can act as selective

immunosuppressants. We do not understand the mechanism whereby the vitamin D hormone

can act as an immunosuppressant especially of T cell-mediated inflammatory responses.

Despite reports to the contrary, there are no in vivo analogs that seem to act without

hypercalcemia. Suppression of autoimmune disease requires not only the active form of vitamin

D and its analogs, but also adequate or high calcium intakes. Further complicating the picture,

little has been done to understand how vitamin D deficiency influences delayed type

hypersensitivity. It is not clear whether the suppression of delayed type hypersensitivity

response seen during vitamin D deficiency is due to the secondary effect of hypocalcemia or isa direct action of vitamin D on certain components of the immune system. This is a complicated

and fertile area of investigation, from which may emerge important new therapies for

autoimmune disease.

View this table:

In this window

In a new window
http://www.fasebj.org/content/15/14/2579.full#ref-37http://www.fasebj.org/content/15/14/2579.full#ref-37http://www.fasebj.org/content/15/14/2579.full#ref-37http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-39http://www.fasebj.org/content/15/14/2579.full#ref-39http://www.fasebj.org/content/15/14/2579.full#ref-39http://www.fasebj.org/content/15/14/2579.full#F9http://www.fasebj.org/content/15/14/2579.full#F9http://www.fasebj.org/content/15/14/2579.full#F10http://www.fasebj.org/content/15/14/2579.full#F10http://www.fasebj.org/content/15/14/2579.full#ref-40http://www.fasebj.org/content/15/14/2579.full#ref-40http://www.fasebj.org/content/15/14/2579.full#ref-40http://www.fasebj.org/content/15/14/2579/T1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/T1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/T1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/T1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/T1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/T1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579.full#ref-40http://www.fasebj.org/content/15/14/2579.full#F10http://www.fasebj.org/content/15/14/2579.full#F9http://www.fasebj.org/content/15/14/2579.full#ref-39http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-37


16/26

Table 1.1,25-(OH)2D3 target cellsa

View larger version:

In this page

In a new window

Figure 1.

Vitamin D receptor (VDR) levels in the immune cells from mice. Mice were fed the Purina chow 5008 diet;lymphocytes were harvested from the spleen and separated into 95% plus pure cells as described by Veldman et al.

(21).


In this page

In a new window

Figure 2.Female B10.PL mice were fed the 0.02% calcium, 0.3% phosphorus-purified diet and immunized with myelin basic

protein together with pertussis toxin. The animals simultaneously received a daily intake of 1,25-(OH)2D3or vehicle.

Even 200 ng/day of 1,25-(OH)2D3does not markedly reduce the incidence of EAE under low dietary calcium

conditions.
http://www.fasebj.org/content/15/14/2579/F1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579/F2.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F2.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F2.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F2.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F2.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F2.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F2.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F2.expansion.htmlhttp://www.fasebj.org/content/15/14/2579.full#ref-21http://www.fasebj.org/content/15/14/2579/F1.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F1.expansion.html


17/26


In this page

In a new window

Figure 3.1,25-(OH)2D3is fully effective in preventing EAE in mice fed a 1% calcium, 0.3% phosphorus diet. A detailed

description of the methods is found in Cantorna et al. (27).

View larger version: In this page

In a new window

Figure 4.1,25-(OH)2D3prevents collagen-induced arthritis. Male DBA/1LacJ mice were fed a 0.02% calcium, 0.3%

phosphorus diet. Following the immunization procedure with bovine collagen type II, animals were treated with

either vehicle or vehicle containing 50 ng/day of 1,25-(OH)2D3mixed in the diet. Mice were observed daily and

began to show symptoms 30 days postimmunization. Treated animals showed no symptoms (see Cantorna et al.,

ref 30).


In this page

In a new window
http://www.fasebj.org/content/15/14/2579/F3.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F3.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F3.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F3.expansion.htmlhttp://www.fasebj.org/content/15/14/2579.full#ref-27http://www.fasebj.org/content/15/14/2579.full#ref-27http://www.fasebj.org/content/15/14/2579.full#ref-27http://www.fasebj.org/content/15/14/2579/F4.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F4.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F4.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F4.expansion.htmlhttp://www.fasebj.org/content/15/14/2579.full#ref-30http://www.fasebj.org/content/15/14/2579.full#ref-30http://www.fasebj.org/content/15/14/2579.full#ref-30http://www.fasebj.org/content/15/14/2579/F5.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F5.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F5.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F5.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F5.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F4.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F3.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F5.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F4.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F3.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F5.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F4.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F3.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F5.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F5.expansion.htmlhttp://www.fasebj.org/content/15/14/2579.full#ref-30http://www.fasebj.org/content/15/14/2579/F4.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F4.expansion.htmlhttp://www.fasebj.org/content/15/14/2579.full#ref-27http://www.fasebj.org/content/15/14/2579/F3.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F3.expansion.html


18/26

Figure 5.MRL/MJP mice were fed the 0.87% calcium, 0.3% phosphorus-purified diet throughout. Controls received vehicle

incorporated into the diet or the indicated dose of 1,25-(OH) 2D3dissolved in the vehicle and added to the diet to

provide 50 ng/day/mouse or 100200 ng/day. Symptoms of lupus and proteinuria were prevented by this treatment.


In this page

In a new window

Figure 6.MRL/MJP mice fed a 0.02% calcium diet were not protected by treatment with 1,25-(OH) 2D3at 100 ng/mouse/day.

This treatment in fact accelerated the appearance of lesions.


In this page

In a new window

Figure 7.IL-10 knockout mice were fed the 0.87% calcium, 0.3% phosphorus diet for 10 wk and the small intestine was

weighed at the end of the experiment. The data are supported by histology scores and declines in body weight. The

results illustrate that 1,25-(OH)2D3prevents the enterocolitis produced by a deficiency of IL-10.
http://www.fasebj.org/content/15/14/2579/F6.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F6.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F6.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F6.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F7.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F7.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F7.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F7.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F8.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F7.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F6.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F8.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F7.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F6.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F8.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F7.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F6.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F7.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F7.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F6.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F6.expansion.html


19/26


In this page

In a new window

Figure 8.Incidence and severity of type I diabetes developed in NOD mice. Weanling NOD mice were fed the purified 0.87%

calcium, 0.3% phosphorus diet for the entire period and, where indicated, were supplemented with either vitaminD3at 625 ng/day or 1,25-(OH)2D3at 50 ng/day. Type I diabetes was diagnosed by blood glucose rising above 300

mg/100 ml. The results illustrate that vitamin D administration reduces the incidence and severity of the disease,

whereas 1,25-(OH)2D3essentially blocks diabetes in these susceptible mice (33).


In this page

In a new window

Figure 9.1,25-(OH)2D3treatment of B10.PL mice immunized with myelin basic protein and pertussis toxin were given either

vehicle added to the diet or vehicle with 1,25-(OH)2D3(50 ng/day for females and 200 ng/day for males). Upon the

appearance of EAE symptoms in the control group, the animals were killed and lymph nodes were removed for

measurement of TGF-1 transcripts.


In this page

In a new window

Figure 10.1,25-(OH)2D3supplementation markedly increases the transcripts for IL-4 in the lymph nodes of B10.PL mice

immunized with myelin basic protein and pertussis toxin as described in Fig. 9legend.
http://www.fasebj.org/content/15/14/2579/F8.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F8.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F8.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F8.expansion.htmlhttp://www.fasebj.org/content/15/14/2579.full#ref-33http://www.fasebj.org/content/15/14/2579.full#ref-33http://www.fasebj.org/content/15/14/2579.full#ref-33http://www.fasebj.org/content/15/14/2579/F9.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F9.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F9.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F9.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F10.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F10.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F10.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F10.expansion.htmlhttp://www.fasebj.org/content/15/14/2579.full#F9http://www.fasebj.org/content/15/14/2579.full#F9http://www.fasebj.org/content/15/14/2579/F10.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F9.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F10.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F9.expansion.htmlhttp://www.fasebj.org/content/15/14/2579.full#F9http://www.fasebj.org/content/15/14/2579/F10.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F10.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F9.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F9.expansion.htmlhttp://www.fasebj.org/content/15/14/2579.full#ref-33http://www.fasebj.org/content/15/14/2579/F8.expansion.htmlhttp://www.fasebj.org/content/15/14/2579/F8.expansion.html


20/26

In a study published in the journal Nature Immunology, researchers from the University of

Copenhagen found that when a variety of white blood cells known as a T-cell comes across a

pathogen in the bloodstream, it extends a receptor in search of vitamin D. If it encounters the

vitamin, the T cell becomes "activated." If there is not enough vitamin D in the blood, the cell remains

passive and no immune response occurs.

The body produces vitamin D upon exposure to sunlight. It can also be found in eggs, fatty fish,

fortified milk and in supplement form.

Once activated, a T-cell transforms into one of two kinds of cells. One type seeks out and destroys

all traces of the infectious agent, while the other records information about the pathogen and

transmits it to other parts of the immune system. These latter ("helper") cells help the immune

system respond quickly should infection with a similar pathogen occur at a later date.

In addition to providing new information about the importance ofvitamin D,the study provides hope

for better understanding -- and perhaps prevention -- of the unhelpful immune responses that result

in autoimmune disorders like allergies or Type 1 diabetes, as well as those that cause the body toreject transplanted organs. The researchers were able to determine what chemical steps occur to

transform a T-cell from active to inactive, suggesting the possibility that doctors may eventually be

able to initiate or block this process, depending on the patient's need.

Sources for this story include:

http://news.ku.dk/all_news/2010/2010.3/d_vitamin/; http://www.dailymail.co.uk/health/article-

1256149/Sunshine-play-vital... .
http://www.naturalnews.com/vitamin_D.htmlhttp://www.naturalnews.com/vitamin_D.htmlhttp://www.naturalnews.com/vitamin_D.htmlhttp://news.ku.dk/all_news/2010/2010.3/d_vitamin/;http://news.ku.dk/all_news/2010/2010.3/d_vitamin/;http://www.dailymail.co.uk/health/article-1256149/Sunshine-play-vital-role-in.htmlhttp://www.dailymail.co.uk/health/article-1256149/Sunshine-play-vital-role-in.htmlhttp://www.dailymail.co.uk/health/article-1256149/Sunshine-play-vital-role-in.htmlhttp://www.dailymail.co.uk/health/article-1256149/Sunshine-play-vital-role-in.htmlhttp://www.dailymail.co.uk/health/article-1256149/Sunshine-play-vital-role-in.htmlhttp://news.ku.dk/all_news/2010/2010.3/d_vitamin/;http://www.naturalnews.com/vitamin_D.html


21/26

Vitamin A and Its Effects on ImmuneSystem

LEAVE YOUR OPINION

LOG INTO VOTE:

Vitamin A is one of the major vitamins that play a crucial role in the health of

the eyes. It also helps in formation and maintenance of teeth, soft tissues, and

skin. Its role in the immune system is

being widely researched.

Vitamin A play a crucial role in the

health of the eyes

It has been noted to function in coordination with

other vitamins and minerals in the regulation of

the immune system. Some of the areas where

vitamin A plays a vital role in the immune system

are discussed in the below sections.

Action againstMeasles Virus

A study performed in Canada evaluated the ability of vitamin A to reduce the death rate associated

with the measles virus. The measles virus replicates by affecting the cell signaling in our body wherein

the affected cells are not able to send warning signs.Administration of vitamin A was noted to block

this effect of the measles virus by strengthening the immune cells. Vitamin A improves the functioning

of the uninfected cells and makes them resistant to the viral replication. This effect of vitamin A can

help to augment the effects of the vaccinations or antiviral drugs being administered to counter viral

infections. Boosting of the cells ability to resist an infection and improving the cell signaling

mechanisms helps in reducing the virulence (infective capability) of a virus.1

Vitamin A Promotes T-lymphocytes and Associated Cells

Administration of vitamin A helps the progression of certain components of the T- lymphocytes. It was

noted that the concentration of certain proteins related to the T-cells was significantly increased

following administration of vitamin A supplements. The functioning of other immune cells known as

monocots was also increased. Furthermore, the concentration of natural killer (NK) cells and T-helper

cells in the blood were noted to increase as levels of vitamin A increased. These cells play a vital role
http://www.steadyhealth.com/articles/Vitamin_A_and_Its_Effects_on_Immune_System_a1574.html#comment-boxhttp://www.steadyhealth.com/articles/Vitamin_A_and_Its_Effects_on_Immune_System_a1574.html#comment-boxhttp://www.steadyhealth.com/index/login/http://www.steadyhealth.com/index/login/http://terms.steadyhealth.com/Measles_virushttp://terms.steadyhealth.com/Measles_virushttp://terms.steadyhealth.com/Measles_virushttp://terms.steadyhealth.com/Measles_virushttp://www.steadyhealth.com/index/login/http://www.steadyhealth.com/articles/Vitamin_A_and_Its_Effects_on_Immune_System_a1574.html#comment-box


22/26

in maintaining the anticancer and antiviral ability of the immune system.2

Several other studies have reported that vitamin A has a role in the regulation of the genes and

proteins controlling the activation of T-cells and the production of cytokines. Adequate amounts of

vitamin A in the body helps in better functioning of these processes and thereby improves the

immunity of an individual.2, 3

Retinoic Acid and Phagocytes

Retinoic acid is a derivative of vitamin A which helps in the growth and development of the bone and

skin cells. Retinoic acid is required for the production and regulation of B- lymphocytes by the cells

present in the cells lining thedigestive tract. Further role of vitamin A has also been noted in the

maturation of the phagocytes in the bone marrow. A deficiency of vitamin A can hamper these

functions leading to decreased accumulation of B- lymphocytes and production of immature

phagocytes that would weaken theimmune response.

Vitamin B6 Strengthens Immune Response COMMENTS (1) LEAVE YOUR OPINION

LOG INTO VOTE:

Vitamins are among the most essential nutrients required for the

optimalfunctioning of our body, and adequate intake of vitamins and other

micronutrients areessential forthe efficientfunctioningof the immunesystem.

Deficiencies of several vitamins includingvitamin

B6 are associated with a number of disorders

related to immune function.

Strengthening Immune Responses

Vitamin B6 works along with other vitamins and

micronutrients to support the protective activities

being undertaken by the immune cells. Deficiency

of essential vitamins such as B6 has been

associated with suppression of the immunity function which predisposes individuals to infectious

disorders. This may be beneficial in individuals falling under the high risk category for immune

disorders. Children, older adults, individuals suffering immune disorders are noted to have a weakened
http://terms.steadyhealth.com/Digestive_tracthttp://terms.steadyhealth.com/Digestive_tracthttp://terms.steadyhealth.com/Digestive_tracthttp://terms.steadyhealth.com/Immune_responsehttp://terms.steadyhealth.com/Immune_responsehttp://terms.steadyhealth.com/Immune_responsehttp://www.steadyhealth.com/articles/Vitamin_B6_Strengthens_Immune_Response_a1584.html?utm_medium=web&utm_source=steadyhealth&utm_campaign=relArRelArticles#comment-boxhttp://www.steadyhealth.com/articles/Vitamin_B6_Strengthens_Immune_Response_a1584.html?utm_medium=web&utm_source=steadyhealth&utm_campaign=relArRelArticles#comment-boxhttp://www.steadyhealth.com/articles/Vitamin_B6_Strengthens_Immune_Response_a1584.html?utm_medium=web&utm_source

Documents

vitamin in immune system.docx