IL10 in the Normal and Inflamed Gastrointestinal Mucsosa

Thus, it is clear that IL-10 plays a pivotal role in mucosal homeostasis, and that disruption of IL-10 signaling may be involved in the initiation and progression of intestinal inflammation. However, this does not automatically imply a role for IL-10 in the pathogenesis of Crohn's disease. Important questions to be addressed include the levels of IL-10 in inflamed and healthy mucosa, the responsiveness of mucosal mononuclear cells to IL-10, and the presence of functional polymorphisms in genes involved in IL-10 signaling in patients with Crohn's disease.

Several groups have studied serum and tissue levels of IL-10 in patients with active Crohn's disease and healthy controls. Studies of serum IL-10 levels in patients with Crohn's disease and healthy controls have yielded conflicting results.28-30 Furthermore, immunohistochemical studies demonstrate abundant IL-10 protein and mRNA within intestinal epithelial cells of both healthy and inflamed colon.31 However, in patients with active inflammation, IL-10 expression is increased in sub mucosal antigen presenting cells and lamina propria lymphocytes.31 This paradoxical rise in immunoregulatory IL-10 levels in inflamed mucosa should not be surprising given the marked Th1 immune response that is demonstrated. Despite this elevation in endogenous IL-10, lamina propria monocytes isolated from areas of active inflammation still respond to the addition of exogenous IL-10 by reducing the release of pro-inflammatory cytokines such as TNF-a and IL-1 p.2 In addition, a recent report has suggested that low levels of IL-10 mRNA in a non inflamed section of ileum at the time of surgery for active Crohn's disease predict subsequent relapse.32 This suggests that exogenous IL-10 may have a role in suppressing active disease and preventing relapse.

Preliminary data indicate a potential association between disease extent and a functional polymorphism in the promoter region of the IL-10 gene; however, this has not been confirmed in more detailed studies.33-35 Two novel polymorphisms have been reported in the IL-10 receptor 1 gene, a serine 138-to-glycine (S138G) and a glycine 330-to-arginine (G330R) substitution. Despite evidence that the G330R substitution is a loss of function allele, no association has been demonstrated with IBD.36 Thus, at present there is no convincing evidence that genetic polymorphisms in the IL-10 signaling pathway predispose to Crohn's disease.

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