The effects of treadmill and voluntary wheel training on morbidity and inflammation during ulcerative colitis in mice

exercise;inflammation;colitis;stress;forced treadmill running;voluntary wheel running;inflammatory bowel disease.

Cook, Marc

关键词: exercise;    inflammation;    colitis;    stress;    forced treadmill running;    voluntary wheel running;    inflammatory bowel disease.;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/45503/Marc_Cook.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Inflammatory bowel diseases (IBD), such as ulcerative colitis (UC), are causes of chronic morbidity that significantly reduce physical functioning and decrease quality of life in afflicted patients. It is well established that pharmacological anti-inflammatory therapies, aimed to decrease colon inflammation, can attenuate symptoms of UC but their efficacy is not complete and their side effects can be debilitating. Preliminary studies have shown that there is a positive correlation between high levels of physical activity, reduced inflammatory biomarkers, and inflammatory-related disease activity indices. Moderate exercise has been shown to be well tolerated during mild to moderate chronic disease activity and promotes improvements in quality of life, muscle function, bone mineral density, stress management and body composition. This research has been conducted in clinical human studies, making it difficult to explore potential mechanisms through which exercise exerts protective effects. Thus, the purpose of our studies are to examine prior exercise training (30 sessions of treadmill-FTR and 30 days of voluntary wheel running-VWR) effects on morbidity and inflammation in a dextran sodium sulfate (DSS)-induced colitis model in C57Bl/6J mice. We hypothesized that FTR and VWR would improve indices of morbidity and inflammation during colitis. We observed the effects of DSS-induced colitis during a recovery study as mice were euthanized and tissues were harvested on days 6, 8 (disease peak) and 12 in the FTR study and day 8 (disease peak) in the VWR study. We examined indices of morbidity (body weight, food and fluid intake, diarrhea incidence, fecal blood) and colonic inflammation (gene expression and histopathology). Contrary to our initial hypothesis, we found that moderate FTR intensified colonic inflammation as measured by significant (p < 0.05) increases in pro-inflammatory gene expression at disease peak (Day 8). While DSS-treated mice exhibited reductions in food and fluid intake, and body weight, FTR did not significantly exacerbate these symptoms at least through Day 12. Histological assessment confirmed the presence of inflammation and colon damage at Day 6, 8, and 12. Surprisingly, during the 12 day study we observed 3 deaths all in the FTR/DSS group which further confirmed the severity of the inflammatory response exhibited in FTR mice. FTR (in the absence of DSS) increased expression of CCL6 indicating that FTR may increase gut immune surveillance and may be a potential cause of the exacerbated inflammatory response. Immunohistochemical analysis revealed that the number of colonic macrophages increased in FTR mice after training. Therefore we concluded that FTR exacerbates inflammation and causes mortality in this mouse model of colitis and training. Our results demonstrating that FTR resulted in adrenal hypertrophy and thymic involution indicate that, while this training model has demonstrated many physiological benefits, it may be a chronic stressor. In contrast, we observed that VWR significantly reduced morbidity and colonic inflammation in DSS treated mice. This effect was manifest as a significantly lower colon inflammatory burden at disease peak and a faster recovery in body weight, food, and fluid intake in VWR mice. Further, the abundance of colonic lactobacilli was greater in VWR control mice, possibly indicative of an anti-inflammatory mechanism we discussed herein. It is well known that VWR elicits anti-inflammatory effects in many different body compartments that are immunologically challenged (e.g. adipose tissue and brain) and we add the colon to this list with the data obtained with a mouse model of DSS induced colitis.