Premium
Pivotal roles of interleukin‐6 in transmural inflammation in murine T cell transfer colitis
Author(s) -
Kitamura Kazuya,
Nakamoto Yasunari,
Kaneko Shuichi,
Mukaida Naofumi
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0604328
Subject(s) - biology , inflammation , colitis , immunology , interleukin , adoptive cell transfer , microbiology and biotechnology , t cell , cytokine , immune system
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‐α, interferon‐γ, 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.