Authors: Kanai T, Watanabe M, Okazawa A, Sato T, Yamazaki M, Okamoto S, Ishii H, Totsuka T, Iiyama R, Okamoto R, Ikeda M, Kurimoto M, Takeda K, Akira S, Hibi T.
Institution: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
Background: Crohn's disease (CD) is associated with an increased number of infiltrating macrophages, which release a variety of proinflammatory cytokines. Interleukin (IL)-18 has been implicated in the modulation of mucosal CD4(+) T cells towards Th1 responses, which are implicated in the pathogenesis of CD. Here we assess the role of macrophages and of IL-18 in the murine model of intestinal inflammation that mimics the immunologic characteristics of human CD.Results: The colonic mucosa of TNBS-treated mice was marked by infiltration of Mac-1-positive macrophages and up-regulation of IL-18. The administration of the anti-Mac-1-saporin antibody or the neutralizing anti-IL-18 antibody resulted in a dramatic attenuation of mucosal inflammation in this model. In addition, TNBS was unable to induce significant colitis in the IL-18(-/-) mice.
Conclusions: Our data underscore the pivotal role of macrophages, and the macrophage-derived IL-18, in the establishment of TNBS-induced colitis in mice. Our results highlight the potential use of therapy directed against IL-18 in the treatment of patients with CD.
Related Studies:
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- Macrophage-Derived IL-18-Mediated Intestinal Inflammation in the Murine Model of Crohn's Disease
- Interleukin 16 is Up-Regulated in Crohn's Disease and Participates in TNBS Colitis in Mice
