Published online before print August 31, 2004

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(Journal of Leukocyte Biology. 2004;76:1111-1117.)
© 2004 by Society for Leukocyte Biology

Pivotal roles of interleukin-6 in transmural inflammation in murine T cell transfer colitis

Kazuya Kitamura^*,,1, Yasunari Nakamoto^*, Shuichi Kaneko^* and Naofumi Mukaida

^* Department of Gastroenterology, Graduate School of Medical Science,
Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Japan

¹ Correspondence: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Takara-machi 13-1, Kanazawa 920-8641, Japan. E-mail: kkitamura{at}medf.m.kanazawa-u.ac.jp

Breakdown of normal mucosal immunity is one of the major causes for inflammatory bowel disease. Interleukin (IL)-6 is a proinflammatory cytokine produced aberrantly in various types of inflammation, but its role in inflammatory bowel disease is still obscure. Hence, we analyzed the roles of IL-6 in the pathogenesis of murine T cell transfer colitis, whose histopathology resembles Crohn’s disease. The transfer of CD4⁺CD45RB^high T cells into severe combined immunodeficiency mice induced the infiltration of T cells and macrophages, and the gene expression of CC chemokine receptor (CCR)1, CCR2, CCR5, CXC chemokine receptor 3, their ligands, tumor necrosis factor-, interferon-, and IL-6 was progressively augmented as colitis developed. The incidence of transmural colitis was significantly reduced with a minimal decrease in the severity of colitis in recipients transferred with CD4⁺CD45RB^high T cells derived from IL-6-deficient mice compared with those with wild-type mice. Moreover, the gene expression of several cytokines, chemokines, and matrix metalloproteinases was reduced significantly in recipients transferred with IL-6-deficient, mice-derived T cells. These observations suggested that T cell-derived IL-6 may augment the gene expression of several proinflammatory molecules, thereby causing transmural inflammation. Thus, IL-6 might be a promising target for treating transmural inflammation in Crohn’s disease, which can lead to severe complications such as strictures, fissures, and fistulas.

Key Words: inflammatory bowel disease • animal model • chemokine • matrix metalloproteinase

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