"stress is detrimental and moderate exercise is beneficial to lupus nephritis pathogenesis:...
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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
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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.
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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
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Blood Urea Nitrogen Levels at 32 Weeks
Exercise
Non-Exercise
BUN
Leve
l Rel
ative
to B
asel
ine
*
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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
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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
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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
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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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