IL-10 therapy in Crohn's disease: at the crossroads

I nterleukin 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