IBD - PROGRESS IN PATHOGENESIS

Limited progress has occurred in the search for new etiological agents . Trials with antituberculous drugs appear to benefit some patients wi th Crohn's disease, but isolation of Mycobacterium johnei from tissues continues to be sporadic. Genetic heterogeneity, suggested by cluster s of patients with the same human leukocyte antigen or autoimmune mark ers, may predispose to inflammatory bowel disease (IBD). Identificatio n of dominant regions of the T cell receptor is being actively pursued with the hope of identifying an immune response to a restricted set o f antigens. The potential relevance of autoantigens has been reinforce d by their detection in the intestine (40 kDa protein) and presence of circulating autoantibodies. Levels of cytokines in the circulation te nd to reflect clinical activity, whereas their presence in the inflame d gut may identify factors responsible for local damage. In addition t o epithelial cells, the role of intestinal fibroblasts, muscle cells a nd endothelial cells in inflammation is being explored. Interest in an imal models of IBD is gaining increasing support, mostly to test inhib itors of inflammation. This expanding knowledge in the pathogenesis of intestinal inflammation is generating new therapies. Lipoxygenase inh ibitors, leukotriene receptor antagonists, cytokine antagonists, new i mmunosuppressors, and antibodies to CD4+ T cells and adhesion molecule s are all under active investigation.