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The Role of IL-10 in Inflammatory Bowel Disease: "Of Mice and Men"

Schering-Plough Research Institute, Lafayette, New Jersey 07848, michael.leach{at}spcorp.com.

Natalie J. Davidson

DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304

Madeline M. Fort

DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304

Fiona Powrie

University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom

Donna M. Rennick

DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304

Inflammatory bowel disease (IBD) is a generic term typically used to describe a group of idiopathic inflammatory intestinal conditions in humans that are generally divided into Crohn's disease and ulcerative colitis. Although the etiology of these diseases remains unknown, a number of rodent models of IBD have recently been identified, all sharing the concept that the development of chronic intestinal inflammation occurs as a consequence of alterations in the immune system that lead to a failure of normal immunoregulation in the intestine. On the basis of these models, it has been hypothesized that the development of IBD in humans may be related to a dysregulated immune response to normal flora in the gut. Immunodeficient scid mice injected with CD4⁺ CD45RB^high T cells and mice deficient in interleukin (IL)-10 (IL-10^-/-) are among the rodent models of IBD. In both models, there is inflammation and evidence of a Th1-like response in the large intestine, characterized by CD4⁺ T-cell and macrophage infiltrates, and elevated levels of interferon-. Because IL-10 is an immunomodulatory cytokine that is capable of controlling Thl-like responses, the role of IL-10 was investigated in these models. IL-10 was shown to be important in regulating the development of intestinal inflammation in both models. These results provided key data that supported initiation of clinical trials evaluating the efficacy of IL-10 in patients with IBD.

Key Words: Interleukin-10 • Th1 • colitis • T cell • mucosal immunity

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