Mechanisms of tissue damage in inflammatory bowel disease

Abstract

Crohn disease and ulcerative colitis are caused by an excessive immune-inflammatory reaction in the intestinal wall. Analysis of the types of immune response ongoing in the inflamed intestine has revealed that in Crohn disease there is predominantly a T helper cell type 1 response, with exaggerated production of interleukin (IL)-12 and interferon-gamma, whereas in ulcerative colitis the lesion seems to be more of an antibody-mediated hypersensitivity reaction. Despite these differences, downstream inflammatory events are probably similar in both conditions. In both Crohn disease and ulcerative colitis there is an increased synthesis of proinflammatory cytokines, including IL-1beta, IL-6, IL-8, IL-16, and tumor necrosis factor-alpha accompanying the influx of nonspecific inflammatory cells into the mucosa. These cytokines contribute to the tissue damage either directly or indirectly by enhancing the production of matrix metalloproteinases and growth factors, which produce ulceration as well as mucosal repair.