Immune response in mouse experimental cholangitis associated with colitis induced by dextran sulfate sodium

Background and Aim: Primary sclerosing cholangitis is frequently complicated by inflammatory bowel disease. Although many colitis models have been reported, little information has been obtained about complicated cholangitis. The aim of the present study was to determine whether hepatobiliary disorders occur in mice experimental colitis, and to clarify the underlying mechanisms. Methods: The CD-1 mice were fed standard chow with or without dextran sulfate sodium in the drinking water, followed by histological examination of the liver and colon. Mononuclear cells were isolated from these organs, and cytokine production was assessed. The CD4/CD8 ratio and the population of natural killer T (NKT) cells were analyzed by flow cytometry. Results: Inflammatory cell infiltration and focal necrosis in the liver were found in 33% of treated mice. In treated mice, the CD4/CD8 ratio increased in the liver, whereas no such change was found in the colon. Also an increase of interferon-gamma and a decrease of interleukin-4 production were observed. The NKT cell population showed transient changes in the liver and colon. Conclusions: Hepatobiliary disorders were complicated with experimental colitis in CD-1 mice. Immunological findings indicate a T-helper-1-dominant underlying mechanism, and NKT cells may play a pathogenic role in this model. This model may help to elucidate the relationship between hepatic and colonic inflammations. (C) 2004 Blackwell Publishing Asia Pty Ltd.