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

Biochem Biophys Res Commun. 2005 Nov 18;337(2):647-54. doi: 10.1016/j.bbrc.2005.09.107. Epub 2005 Sep 26.


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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / chemically induced*
  • Colitis / pathology
  • Dextran Sulfate
  • Gene Expression / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Humans
  • Inflammatory Bowel Diseases / pathology*
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Macrophages, Peritoneal / metabolism
  • Mice
  • RNA, Messenger / genetics
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Dextran Sulfate