The role of IL-10 in inflammatory bowel disease: "Of mice and men"

Inflammatory bowel disease (IBD) is a generic term typically used to descri be 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 deve lopment of chronic intestinal inflammation occurs as a consequence of alter ations in the immune system that lead to a failure of normal immunoregulati on 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 imm une 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, ch aracterized by CD4(+) T-cell and macrophage infiltrates, and elevated level s of interferon-gamma. Because IL-IO is an immunomodulatory cytokine that i s capable of controlling Th1-like responses, the role of IL-IO was investig ated in these models. IL-10 was shown to be important in regulating the dev elopment of intestinal inflammation in both models. These results provided key data that supported initiation of clinical trials evaluating the effica cy of IL-10 in patients with IBD.