"Stress is Detrimental and Moderate Exercise is Beneficial to Lupus Nephritis Pathogenesis: Extra-Medicinal Influences on Chronic Autoimmune Inflammation"
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Presented this work as a poster tour presentation at The European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology meeting June 10-13, 2015 in Rome, Italy. Awarded a travel bursary to attend this conference.
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"Stress is Detrimental and Moderate Exercise is Beneficial to Lupus Nephritis Pathogenesis: Extra-Medicinal Influences on Chronic Autoimmune Inflammation"
- 1. Stress is Detrimental and Moderate Exercise is Beneficial to Lupus Nephritis Pathogenesis: Extra-Medicinal Influences on Chronic Autoimmune Inflammation 1
- 2. Chronic inflammation contributes to the pathogenesis of many diseases 2 Chronic inflammation CVD Atherosclerosis Cardiomyopathy Heart failure Stroke Autoimmunity Rheumatoid arthritis Lupus Sjogren’s syndrome Diabetes IBD Psoriasis Cancer Lung Colon Pancteatic lymphoma Neurological Disorders Alzheimer’s Parkinson’s ALS Metabolic Disorder Complications Fatty liver disease Heart disease Bone, musculoskeletal disease Osteoporosis Osteoarthritis Muscular dystrophy
- 3. 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 3
- 4. Background Exercise 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 responses Effects of exercise are transient Lost after 36-48 hours Suggests greatest benefits achieved with daily exercise 4
- 5. BUN Levels Increase and Weight Decreases in NZM Mice with Disease Progression 5 NZM 2410 Mouse (develops lupus nephritis from 22- 40 weeks of age) -0.5 0.5 1.5 2.5 3.5 4.5 5.5 6.5 23 25 27 29 31 33 BUNandWeight RelativetoBaseline Age (Weeks) Weight BUN Removal Criteria Mice that lost 20% or more of their body weight and found to have BUN levels over 50 mg/dL were sacrificed.
- 6. Effects of exercise on lupus nephritis 6 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
- 7. 7 Effects of Exercise in Lupus Nephritis 0 2 4 6 8 10 12 14 16 BUNLevelRelativetoBaseline Blood Urea Nitrogen Levels at 32 Weeks Exercise Non-Exercise *
- 10. 10 Immunohistochemistry Identifies Macrophage Infiltrate in Kidneys of Non-exercise Mice
- 11. Effects of social stress on lupus nephritis Aggressor 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
- 12. Effects of Stress in Lupus Nephritis 12
- 13. Histopathology shows that stressed mice exhibit enhanced pathology 13
- 14. • 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 14 CONCLUSIONS
- 15. 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 15
Editor's Notes
- It is well-known that chronic levels of inflammation (both low and high levels) are present and contributing factors leading to the pathogenesis of many diseases. These disorders cover a broad spectrum and include cardiovascular disease (CVD), autoimmune disorders, neurological disorders, bone and musculoskeletal diseases, complications associated with metabolic disorders, and even cancer. Furthermore, many studies have shown the positive effects of exercise in the management and clinical outcome of many of these same diseases.
- Despite this strong correlation between inflammation and exercise, the exact explanation of how exercise is effecting these diseases still remains unclear. Additionally, an animal model to study the systemic effects of exercise over inflammation is currently lacking. Thus, we set out to explore the following hypothesis in this study: that exercise can regulate inflammation by systemic suppression and that this effect would eventually be lost over time.
- In conclusion, we suggest that moderate exercise could therefore be a very potent therapeutic intervention to be used to control the inflammation associated with a variety of different diseases, but is unfortunately a tremendously underutilized therapeutic modality in clinical practice today. Also, we have demonstrated that exercise is a robust and systemic biological response modifier that can subsequently serve to regulate inflammation. Lastly, we have shown that the effects of exercise in modulating these responses are completely lost after 36-48 hours, which suggests that the greatest benefits may be achieved with a daily exercise routine.