Pathogenesis of inflammatory bowel disease

In spite of expanding knowledge of cellular and molecular mechanisms of int estinal inflammation, the etiology and pathogenesis of inflammatory bowel d isease (IBD) remain obscure. The link between the environment and IBD is st ill circumstantial, but definite progress is occurring in defining genetic susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC). T he notion that normal enteric flora play a role in initiating or maintainin g IBD is gaining momentum. Some components of the flora may act as noxious agents, whereas others (probiotics) seem to have a protective effect. The i mportance of the mucosal immune system to IBD is established, and evidence is accumulating that nonimmune components, such as epithelial, mesenchymal, and endothelial cells, also contribute to gut inflammation. The effect of cytokines in intestinal immunity is being elucidated by studies on their mo lecular mechanism, particularly the activation of nuclear factor (NF)-kappa B. Finally, the beneficial effects of cytoprotective prostaglandins and ce ll adhesion molecule (CAM) blockade promise novel therapeutic opportunities derived from an improved understanding of IBD pathogenesis. (C) 1999 Lippi ncott Williams & Wilkins, Inc.