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- Crohn's disease
- inflammatory bowel disease
- inflammation
- interleukin 10
- neopterin
- interferon γ
- Crohn's disease
- infliximab
- tumour necrosis factor
Treatment of Crohn's disease with the anti-inflammatory cytokine interleukin 10
Interleukin 10 (IL-10) was initially discovered and isolated on the basis of its ability to suppress cytokine synthesis by Th1 helper cells. Macrophages and their secreted mediators are the primary target of IL-10. IL-10 downregulates expression of class II and B7 molecules, as well as IL-12 production, thus impairing the macrophage dependent stimulation of antigen reactive Th-1 cells.1
The important regulatory role of IL-10 in the gut became obvious when IL-10 deficient mice (IL-10−/−), generated by gene targeting, developed chronic enterocolitis.2 More interestingly, IL-10−/− mice kept under germfree conditions do not develop enterocolitis, which suggests that in the absence of the immunomodulatory effects of IL-10, an unrestricted intestinal inflammatory response develops towards normal enteric antigens. The observations in the IL-10−/− mice lay the foundation for administration of IL-10 in several animal models. The results of these studies clearly showed prevention of intestinal inflammation by IL-10, mainly by downregulation of an intestinal proinflammatory Th1 response. However, systemic IL-10 administration was successful only when administered prior to the initiation of colitis but was ineffective at reversing any established inflammation.3,4
IL-10: THE CLINICAL EXPERIENCE
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