Inflammatory bowel disease (IBD) is an immunologically mediated disorder that is characterized by chronic, relapsing, and inflammatory responses. Dextran sulfate sodium (DSS)-induced experimental colitis in mice has been recognized as a useful model for human IBD and interleukin (IL)-1 beta is a key cytokine in the onset of IBD. The purpose of the present study was to clarify which pro-inflammatory mediators are targeted by IL-1 beta in mice with DSS-induced colitis. First, we found that DSS markedly induced IL-1 beta production in both dose- and time-dependent manners (P < 0.05 and P < 0.01, respectively) in murine peritoneal macrophages (pM phi), while that of tumor necrosis factor-alpha was insignificant. Further, the expressions of mRNA and protein for IL-1 beta were increased in colonic mucosa and pM phi from mice that received drinking water containing 5% DSS for 7 days (P < 0.01, each). In addition, the expressions of IL-6, granulocyte macrophage-colony stimulating factor, inducible nitric oxidesynthase, and cyclooxygenase-2 mRNA were also time dependently increased (P < 0.01, each). Furthermore, administration of rIL-1 beta (10 mu g/kg, i.p.) significantly induced the expressions of IL-1 beta and IL-6 mRNA in colonic mucosa from non-treated mice (P < 0.01). Anti-mIL-1 beta antibody treatments (50 mu g/kg, i.p.) attenuated DSS-induced body weight reduction and shortening of the colorectum (P < 0.05, each), and abrogated the expressions of IL-I beta and IL-6 mRNA in colonic mucosa (P < 0.01, each). Our results evidently support the previous findings that IL-1 beta is involved in the development of DSS-induced experimental colitis in mice, and strongly suggest that IL-1 beta targets itself and IL-6 for progressing colonic inflammation. (c) 2005 Elsevier Inc. All rights reserved.