| First Author | Kitamura K | Year | 2004 |
| Journal | J Leukoc Biol | Volume | 76 |
| Issue | 6 | Pages | 1111-7 |
| PubMed ID | 15339938 | Mgi Jnum | J:94173 |
| Mgi Id | MGI:3511412 | Doi | 10.1189/jlb.0604328 |
| Citation | Kitamura K, et al. (2004) Pivotal roles of interleukin-6 in transmural inflammation in murine T cell transfer colitis. J Leukoc Biol 76(6):1111-7 |
| abstractText | 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-alpha, interferon-gamma, 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. |
