Effects of Azithromycin on Behavior, Pathologic Signs, and Changes in Cytokines, Chemokines, and Neutrophil Migration in C57BL/6 Mice Exposed to Dextran Sulfate Sodium.

Here we characterized the murine dextran sulfate sodium (DSS) model of acute colitis. Specifically, we evaluated azithromycinand metronidazole treatment regimens to assess their effects on animal wellbeing, pathologic changes, barrier function,cytokine and chemokine profiles, and neutrophil migration in colon tissue. Azithromycin treatment significantly reduced theseverity of colitis, as assessed through body weight change, water consumption, macroscopic lesions, and animal behaviors(activity level, climbing, and grooming), but did not alter food consumption or feeding behavior. Mucosal barrier function(evaluated by using FITC-labeled dextran) was decreased after DSS exposure; azithromycin did not significantly alter barrierfunction in mice with colitis, whereas metronidazole exacerbated the colitis-related deficit in barrier function. In addition,metronidazole appeared to exacerbate disease as assessed through water consumption and animal behaviors (overall activity,climbing, grooming, and drinking) but had no effect on weight loss, macroscopic lesions, or eating behavior. Pathologicchanges were typical for DSS treatment. Antibiotic treatment resulted in reduced levels of proinflammatory cytokines andchemokines and decreased neutrophil adhesion and emigration in DSS-exposed mice. The results highlight the importanceof clinical and behavioral assessments in addition to laboratory evaluation as tools to evaluate animal welfare and therapeuticefficacy in disease models. Data from this study suggest that azithromycin may convey some benefits in the mouse DSS colitismodel through modulation of the immune response, including neutrophil migration into tissues, whereas metronidazolemay exacerbate colitis.