Interleukin-1β targets interleukin-6 in progressing dextran sulfate sodium-induced experimental colitis

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)-1β 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-1β in mice with DSS-induced colitis. First, we found that DSS markedly induced IL-1β production in both dose- and time-dependent manners (P < 0.05 and P < 0.01, respectively) in murine peritoneal macrophages (pMϕ), while that of tumor necrosis factor-α was insignificant. Further, the expressions of mRNA and protein for IL-1β were increased in colonic mucosa and pMϕ 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 oxide synthase, and cyclooxygenase-2 mRNA were also time dependently increased (P < 0.01, each). Furthermore, administration of rIL-1β (10 μg/kg, i.p.) significantly induced the expressions of IL-1β and IL-6 mRNA in colonic mucosa from non-treated mice (P < 0.01). Anti-mIL-1β antibody treatments (50 μg/kg, i.p.) attenuated DSS-induced body weight reduction and shortening of the colorectum (P < 0.05, each), and abrogated the expressions of IL-1β and IL-6 mRNA in colonic mucosa (P < 0.01, each). Our results evidently support the previous findings that IL-1β is involved in the development of DSS-induced experimental colitis in mice, and strongly suggest that IL-1β targets itself and IL-6 for progressing colonic inflammation.