Involvement of interleukin-1 in the development of ulcerative colitis induced by dextran sulfate sodium in mice

Dextran sulfate sodium (DSS)-induced colitis in mice has been recognized as a model for human ulcerative colitis. Using this model, the effects of anti-murine interleukin 1 beta (IL-1 beta) antibodies (anti-muIL-1 beta) and recombinant murine IL-1 receptor type I (rmuIL-1R) on the development of colitis were examined to determine whether IL-1 plays a role in colitis. Furthermore, RT-PCR amplification was used to examine for the presence of mRNAs for IL-1 alpha and IL-1 beta in the large intestine. In mice with colitis induced by DSS, administration of anti-muIL-1 beta (5 mg/kg, once/week, i.p.) significantly suppressed body weight loss and shortening of the large intestine. Administration of rmuIL-1R (0.2 mg/kg or 1.0 mg/kg, once/day, i.v.) significantly suppressed shortening of the large intestine. Expression of mRNAs for IL-1 alpha and IL-1 beta was observed in the large intestine of mice which received distilled water containing 3% DSS for 5 days. The expression tended to increase in mice which received DSS for 11 days. In contrast, mRNA expression was not observed in mice which received distilled water without DSS, These results clearly demonstrate that IL-1 is involved in the development of DSS-induced colitis in mice and suggest that downregulation of IL-1 might be useful for the treatment of patients with ulcerative colitis. (C) 1998 Academic Press.