Establishment and validation of a new semi-chronic dextran sulfate sodium-induced model of colitis in mice

Background: The dextran sulfate sodium (DSS)-induced model of colitis is a commonly used model of inflammatory bowel disease (IBD) in animals. However, there were few studies on the therapeutic efficacy of drugs for IBD after the onset of colitis in this model. We established a semi-chronic model of DSS-induced colitis in mice and used it to assess the therapeutic efficacy of agents for IBD. Materials and methods: Colitis was induced by administration of 3% DSS in drinking water to mice for 7 days followed by 5 days of normal drinking water. Results: Ulcerative colitis (UC)-like symptoms including diarrhea, bloody stools and body-weight loss were observed from days 3 to 5, and continued until day 12 after DSS administration. Persistent colitis was associated with sustained local production of cytokines and was characterized by infiltration of inflammatory cells, crypt loss and erosion in the distal colon. These features are similar to those found in patients with UC. In this model, anti-tumor necrosis factor (TNF)-alpha antibody or anti-interleukin (IL)-12/23p40 antibody significantly ameliorated colitis when administered after the onset of colitis. However, treatment with FK506, prednisolone or sulfasalazine provided limited therapeutic benefit. Conclusion: The DSS-induced colitis established here showed similar symptomatic and histopathological features to those seen in human UC. This model may be available for predicting the clinical efficacy of candidate compounds for UC. (C) 2012 Elsevier B.V. All rights reserved.