IBD: Progress in pathogenesis

Limited progress has occurred in the search for new etiological agents. Trials with antituberculous drugs appear to benefit some patients with Crohn's disease, but isolation of Mycobacterium johnei from tissues continues to be sporadic. Genetic heterogeneity, suggested by clusters of patients with the same human leukocyte antigen or autoimmune markers, may predispose to inflammatory bowel disease (IBD). Identification of dominant regions of the T cell receptor is being actively pursued with the hope of identifying an immune response to a restricted set of antigens. The potential relevance of autoantigens has been reinforced by their detection in the intestine (40 kDa protein) and presence of circulating autoantibodies. Levels of cytokines in the circulation tend to reflect clinical activity, whereas their presence in the inflamed gut may identify factors responsible for local damage. In addition to epithelial cells, the role of intestinal fibroblasts, muscle cells and endothelial cells in inflammation is being explored. Interest in animal models of IBD is gaining increasing support, mostly to test inhibitors of inflammation. This expanding knowledge in the pathogenesis of intestinal inflammation is generating new therapies. Lipoxygenase inhibitors, leukotriene receptor antagonists, new immunosuppressors, and antibodies to CD4+ T cells and adhesion molecules are all under active investigation.