Stress is Detrimental and Moderate Exercise is Beneficial to Lupus Nephritis Pathogenesis: Extra-Medicinal Influences on Chronic Autoimmune Inflammation

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Chronic inflammation contributes to the pathogenesis of many diseases

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Chronicinflammation

CVDAtherosclerosisCardiomyopathyHeart failureStroke

AutoimmunityRheumatoid arthritisLupusSjogren’s syndromeDiabetesIBDPsoriasis

CancerLungColonPancteaticlymphoma

Neurological DisordersAlzheimer’sParkinson’sALS

Metabolic DisorderComplicationsFatty liver diseaseHeart disease

Bone, musculoskeletaldiseaseOsteoporosisOsteoarthritisMuscular dystrophy

Background The effect of exercise over inflammatory diseases

remains unclear Model displaying the systemic effects of exercise is

lacking

Hypothesis: exercise can suppress inflammation systemically, but its effects are lost over time

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BackgroundExercise could be a very potent therapeutic intervention to control inflammatory disease

Underutilized in clinical practice

Exercise is a robust systemic biological response modifier regulating inflammatory responsesEffects of exercise are transient

Lost after 36-48 hoursSuggests greatest benefits achieved with daily exercise

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BUN Levels Increase and Weight Decreases in NZM Mice with Disease Progression

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NZM 2410 Mouse (develops lupus

nephritis from 22-40 weeks of age)

23 24 25 26 27 28 29 30 31 32 33-0.5

0.5

1.5

2.5

3.5

4.5

5.5

6.5

Weight

BUN

Age (Weeks)

BU

N a

nd W

eigh

t Rel

a-tiv

e to

Bas

elin

e

Removal CriteriaMice that lost 20% or more of their body weight and found to have BUN levels over 50 mg/dL were sacrificed.

Effects of exercise on lupus nephritis

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Exercise = 45 min 9

M/min daily

Submandibular bleeds, biweekly, 100µL of

blood collected, serum isolated. Mice were

weighed weekly.

Blood Urea Nitrogen tests

were completed biweekly using Bioo Scientific BUN Enzymatic

Kit

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Effects of Exercise in Lupus Nephritis

0

2

4

6

8

10

12

Blood Urea Nitrogen Levels at 32 Weeks

Exercise

Non-Exercise

BUN

Leve

l Rel

ative

to B

asel

ine

*

Histopathology Shows Decreased Infiltration in Exercise Group

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Immunohistochemistry Identifies Macrophage Infiltrate in Kidneys of Non-exercise Mice

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Immunohistochemistry Identifies Macrophage Infiltrate in Kidneys of Non-exercise Mice

Effects of social stress on lupus nephritisAggressor mouse

introduced into cage of NZM 2410 males for 2 hours

everyday for 6 days.

Submandibular bleeds, weekly, 100µL of blood

collected, serum isolated. Mice were

weighed weekly.

Blood Urea Nitrogen tests

were completed biweekly using Bioo Scientific

BUN Ezymatic Kit

Effects of Stress in Lupus Nephritis

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Histopathology shows that stressed mice exhibit enhanced pathology

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• Chronic levels of inflammation lead to autoimmune disease pathogenesis

• exercise and stress reduction could be a very potent therapeutic intervention to control the inflammation

• therapeutic to control disease activity• Use in conjunction with clinical treatments

could offer greater success in the management of chronic inflammation in LN

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CONCLUSIONS

Future studies• IL-6 ELISA analysis• Expand these cohorts and repeat/validate data • IRB study to investigate the effects of yoga

• , known to be both moderate exercise and stress reduction

• Arthritis Foundation • therapeutic effects of exercise in animal models of

rheumatoid arthritis, osteoarthritis, and lupus• AstraZeneca

• effects of exercise in an animal model of gout

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