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An antiviral substance & is the first line of defence against
viral attacks.
Term ‘interferon’ orginated from the ‘interference’ of this
molecule on virus replication.
Interferons are a family of host coded proteins produced by
cells on induction by viral or non-viral inducers.
Interferons by itself has no direct action on viruses but it acts
on other cells of the same species, rendering them refractory to
viral infection.
INTERFERONS
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Interferons are inactivated by proteolytic enzymes but not by
nucleases or lipases.
They resist heating at 56-60oC for 30-60mins & stable over a
range of pH 2-10, except gamma IFN which is liable at pH 2.
Mol.wt of 17000 Da - non dialysable & non-sedimentable.
Poorly antigenic, so no routine tests are available for their
detection & estimation.
Interferon assay-based on its biological activity, such as ability
to inhibit plaque formation by sensitive virus.
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Potency of IFN is expressed as International Units(IU) per mL.
Interferons are non-toxic, non-antigenic, diffuses freely in the
body & has a wide spectrum of antiviral activity.
So it is an ideal candidate for use in prophylaxis & treatment of
viral infection.
Interferons are stored at 2 – 8°c
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Proteins in nature & many of them are glycoproteins.
Broadly classified into 3 groups- structure & function.
INTERFERONS
Interferon-α
(INF-α)
Interferon-β
(INF-β)
Interferon-γ
(INF-γ)
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Alpha interferon
• Also known as Leukocyte interferon.
• Produced by leukocytes following induction by suitable
viruses.
• Non-glycosylated protein.
• Atleast 16 antigenic subtypes have been identified.
Beta interferon
• Fibroblast interferon.
• Produced by fibroblasts & epithelial cells following stimulation
by viruses or polynucleotides.
• Is a glycoproteins.
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Gamma interferon
• Immune interferon
• Produced by T-lymphocytes on stimulation by antigens or
mitogens.
• Is a glycoprotein.
• More concerned with immunomodulatory & antiproliferative
functions than with antiviral defence.
• It also differs from alpha & beta interferons in having a
separate cell receptor.
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GENERAL ACTION OF INTERFERONS
Tissue cell is infected by a virus
Releases interferon
Interferon will diffuse to the surrounding
cells & binds with receptor.
Production of a protein that prevents the
synthesis of viral proteins.
Prevents the spread of the virus
throughout the body.
PRODUCTION OF RECOMBINANT
INTERFERONS
The complementary DNA(cDNA) was synthesized from mRNA
of a specific interferon.
Inserted to a vector(plasmid) which is introduced into E.coli or
other cells.
IFN can be isolated from culture medium. This is the basic
mechanism of producing recombinant IFNs.
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THERAPEUTIC APPLICATION OF IFNs
Used for treatment of a large no:of viral diseases & cancers.
Alpha IFNs Hepatitis B & C, chronic myeloid leukemia,
multiple myeloma, Kaposi’s sarcoma, melanoma.
Beta IFNs Multiple sclerosis
Gamma IFNs Chronic granulomatous disease, renal cell
carcinoma, chronic myeloid leukemia.
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IFNs cause the death of cancerous cells by stimulating the
action of natural killer(NK) cells, a specialized form of
lymphocytes that can destroy cancer cells.
Also used for the treatment of common cold & influenza. For
this purpose, IFNs can be used as nasal sprays.
Common side effects of IFNs fever, malaise, fatigue,
muscle pains. High levels of IFNs cause kidney, liver, bone
marrow & heart toxicity.11
MARKETED FORMULATIONS
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BRAND NAME TYPE USE
Alferon N Human leukocyte–
derived interferon alfa-
n3
Genital and perianal
warts
Roferon-A Recombinant interferon
alfa-2a
Hairy cell
leukemia,AIDS
Intron A Recombinant interferon
alfa-2b
Hairy cell
leukemia,AIDS
Avonex, Rebif Recombinant interferon
beta-1a
Multiple sclerosis
Betaseron Recombinant interferon
beta-1b
Multiple sclerosis
INTERLEUKINES
These are a large group of cytokines produced mainly by T cells,
although some are also produced by mononuclear phagocytes
(or) by tissue cells.
The interleukins were first described as signals for
communication between white blood cells (leuk- from
leukocytes).
Currently, it is well-known that these molecules are produced and
used as signalling molecules in many cells of the body, in
addition to immune cells.
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Interleukins are secreted rapidly in response to an infectious agent,
it travels to its target cell and binds to the receptor molecule on the
cell’s surface that triggers a cascade of signals within the target cell
altering the cell’s behaviour.
Interleukins represent a broad family of cytokines that are made by
hematopoietic cells and act primarily on leukocytes.
Interleukins are stored at 2 – 8°c
There are currently 35 well-known interleukins, however, there are
many more to be found and characterized.
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MECHANISM OF ACTION AND DOSE
Mechanism of action;
Immunotherapy with IL activates cytotoxic T-cell against RCC
Dose and adminstration;
Interleukin administered via intravenous (iv) injection as high
dose (usually defined as 600,000 – 720,000 units/kg).
Lower dosage iv and subcutaneous IL-2 are also prescribed for
kidney cancer.
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TYPES OF INTERLEUKINES
Interleukin Primary Cell Structure Primary Activities
IL –1α/IL-1β Macrophages, NK Cells, B cells
Inflammation
IL-2 T cells Activates T cells
IL-3 T cells Haematopoietic growth factor
IL-4 T cells B cell growth
IL-5 T cells Eosinophil & B cell growth
IL-6 T cell & fibroblasts Inflammation
IL-7 Stromal cells B & T cell growth
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Continued ……
Interleukin Primary Cell Structure Primary Activities
IL-8 Macrophages Chemoattractant for neutrophils
IL-9 Activated T cells T cell growth & Potentiates IgM, IgG & Ig
E
IL-10 B cells, T cells B cell growth / inhibition of cytokine synthesis by T
cells
IL-11 Bone marrow stromal cells
Haematopoietic co-factor
IL-12 Macrophages, B cells Induction of cell mediated immunity
IL-13 T cells B cell growth
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PRODUCTION OF INTERLEUKINES
•Antigen is internalized and
degraded by the macrophages,
processed, and then presented on
the macrophage surface to the
resting T lymphocyte in conjunction
with an MHC molecule.
•Once the T-cell receptor engages the
MHC molecule plus antigen, the T
cell becomes activated and secretes
IL-2, IL-3, IL-4, IL-5, and IL-6.
•Interleukins 2,4, 5, and 6 enable
activated T cells to undergo clonal
expansion.
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THERAPEUTIC APPLICATION OF
INTERLEUKINES
Used to enhance T-cell activation in immunodeficiency
diseases.
Used in the treatment of cancers and other infectious diseases.
Used to reduce graft rejection.
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MARKETED FORMULATIONS
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BRAND NAME TYPE USE
ALDESLEUKIN Recombinant human IL-
2 (rIL-2)
Chronic hepatitis C,
and Chronic hepatitis B
OPRELVEKIN Recombinant human IL-
11
Hairy cell
leukemia,AIDS
MUPLESTIM IL-3 Hairy cell
leukemia,AIDS
SIGOSIX IL-6 Multiple sclerosis
CONCLUSION
Interferons(IFN) are cytokines that are responsible for the
activity of the immune system .
Interleukins are biologically active glycoproteins derived
primarily from activated lymphocytes and macrophages.
They mediate their action by binding with high affinity to
receptors which belong to a limited number of structural
families
Immunity are produced mainly by activated macrophages
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REFERENCES
Johnson, Howard M., Fuller W. Bazer, Brian E. Szente, et al. "How
Interferons Fight Disease." Scientific American (May 1994): 68–76.
Meulen, Volkerter, N. Stefan. "Inhibition of Major
Histocompatibility Complex Class II-Dependant Antigen
Presentation by Nutralization of Gamma Interferon Leads to
Breakdown of Resistance against Measles Virus-Induced
Encephalitis." Journal of Virology 75 (2000):1–13.
Seppa, Nathan. "Interferon Delays Multiple
Sclerosis." Science News 158 (November 2000): 280–281.
Interferons and Interferon Therapy, R.Priyanka et al /J. Pharm. Sci.
& Res. Vol. 6(12), 2014, 400-40322
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