Animals with Endometriosis Experience Beneficial Effects and Localized Modulation of Cytokine Levels when Exposed to Voluntary Wheel Running

A physically active lifestyle has been shown to confer preventive health benefits in many chronic conditions, in part by enhancing immunological health. Prolonged moderate exercise increases secretion of IL‐6 that may also promote secretion of the anti‐inflammatory cytokine IL‐10. Endometriosis is a chronic gynecological disorder characterized by peritoneal inflammation, chronic pelvic pain, fibrosis, and growth of endometrial tissue outside the endometrial cavity. We recently demonstrated protective effects of prior exercise in this condition, however it is still unclear whether physical activity can alleviate endometriosis that has already developed. Hypothesis Voluntary physical exercise can promote immune strength helping to reduce symptoms in animals with endometriosis. Methods Endometriosis was induced in female Sprague Dawley Rats by implanting four pieces of uterine tissue next to the intestinal mesentery on day 0, while Sham controls received sutures only. Endo (n=11) and Sham controls (Sham; n=11) received no exercise. Another group of endometriosis (EEX; n=10) and sham animals (SHEX; n=10) had access to a running wheel after induction of endometriosis until time of sacrifice at day 60. At sacrifice the developed vesicles, colon, serum and peritoneal fluid were collected and stored for future analysis. Results Endo animals developed vesicles in 79.55% of the implants with an average total area of 71.02±15.50mm 2 and average developed vesicle weight of 0.12±0.04g. No vesicles developed in Sham or SHEX. Endo had significantly increased macroscopic colonic damage (p<0.0001 vs Sham and SHEX). Exposure to exercise significantly decreased the number of vesicles that developed (35.00%, p<0.01), as well as their size (10.23±4.24mm 2 , p<0.01), and weight (0.03±0.01g, p<0.05). EEX had significantly less macroscopic (p<0.0001) and microscopic (p<0.05) colonic damage compared to Endo. Exercise increased the release of various cytokines and chemokines including MIP1 (p<0.01), IL‐10, IP10 (p<0.05), RANTES, and IL‐6 (p<0.05) in peritoneal fluid compared to Endo. Changes in cytokine levels at the systemic level were less pronounced. Conclusions Our results suggest that voluntary physical activity might alleviate endometriosis associated progression of symptomatology, and enhance immune competency by impacting various inflammatory cytokines and angiogenic factors. Taken together, this opens the potential for further exploration of voluntary exercise as a complementary therapy in the patient population for whom current treatments are still non‐curative with many side effects. Support or Funding Information Supported in part by R15AT009915, R25GM082406, U54MD007579.