Immune mechanisms in chronic inflammatory bowel disease

Abstract

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases of unknown etiology. However, there is circumstantial evidence that immune mechanisms play an important role in the pathogenesis of the intestinal lesion, and cytokines produced by lymphoid cells may be critical for the extraintestinal sequelae of the disease. In both Crohn's disease and ulcerative colitis, activation of macrophages seems to be a key feature. Increased production of the macrophage derived cytokines TNF-alpha, IL-1 and IL-6 have been reported in both diseases. Additionally in Crohn's disease, large numbers of activated T lymphocytes can be detected in the lamina propria and the T lymphocyte derived cytokines IL-2 and IFN-gamma are secreted by a higher number of lamina propria T lymphocytes in active Crohn's disease. However, this is not the case in ulcerative colitis. The increased number of activated T lymphocytes secreting IFN-gamma may be responsible for granuloma formation in Crohn's disease, as well as for MHC class II antigen expression on colonic epithelial cells. Lamina propria T lymphocytes seem to have lost their physiological unresponsiveness to several microbial antigens. All these observations suggest that Crohn's disease may be caused by hyperreaction of the local cellular immune system to numerous microbial and nutritional antigens normally present in the intestine. The factor inducing this immune dysregulation remains unknown. Cell-mediated immunity seems to be less important in ulcerative colitis, as activated T lymphocytes are only sparse within the inflamed mucosa, and the T lymphocyte derived cytokines IL- 2 and IFN-gamma cannot be detected in the gut lesion or in the serum. Histopathologic studies also revealed the initial lesion in ulcerative colitis is of the epithelium, and that the inflammatory response seems to be secondary. Increased serum levels of autoantibodies to colonic epithelium and epithelial deposition of immunoglobulins within deposits of complement activation products apically in the colonic epithelium of patients with active ulcerative colitis suggest that ulcerative colitis may be caused by an IgG mediated autoimmune process to colon mucosa.