This site is part of a frame. If you arrived to this page directly, click here ! Crohn's disease Crohn's disease (CD) is a chronic inflammatory disease of the intestines. CD manifests itself by ulcerations in the small and large intestines, but can affect the digestive system anywhere between the mouth and the anus. Little is known about the cause(s) or underlying immunopathogenesis of CD. However, several genes are associated with CD, and mutation(s) in the CARD15/NOD2 gene seems of particular importance; click here for further information. Cytokines such as TNF, FasL, IFN-gamma, IL-2, IL-10 and IL-12 are known to participate in the pathology of CD. The following suggests that IL-10 may be centrally involved:   IL-10 "knock-out" mice consistently develop CD-like disease. If substituted with IL-10, these mice are protected from developing gut inflammation. Macrophage activation with granuloma formation is a hallmark of the pathology of CD, endotoxin (LPS) is a potent activator of macrophages, and a crucial function of IL-10 is to down-regulate macrophage activation. IL-10 therapy has demonstrated efficacy in animal models of CD. Encouraging results have been obtained with IL-10 given to patients with inflammatory bowel disease, both topically in ulcerative colitis and systemically in patients with chronic active CD. As shown in the top figure, IL-10 may play a physiological role in the gut mucosa by its ability to down-regulate macrophage activation induced by LPS released from gram-negative bacteria in the gut. Dysregulation of IL-10 may play a role in the pathogenesis of CD, either because it is produced inappropriately (bottom figure) or in a functionally defective form. Similar pathology may develop if the action of otherwise normally produced IL-10 is prevented, for example if genetic defects in macrophages jeopardize their response to the cytokine. As a result, upregulated production of IFN-gamma contributes to a chronic state of macrophage and T cell activation with granuloma formation. The increased elaboration of IL-1, TNF and Fas ligand (FasL) stimulates the production of toxic reactive oxygen and nitric intermediates (ROI and RNI) in colonocytes and induces apoptosis (cell death).