Etiology and pathogenesis of inflammatory bowel disease

During the past several years both animal and human studies have continued to support a working hypothesis with regard to the immunopathogenic alterations of inflammatory bowel disease (IBD), which lead to the development of chronic intestinal inflammation. Recent findings have provided convincing evidence for the central role of highly activated T helper 1 (Th1) cells due to ineffective downregulation of Th1 cell function. The proinflammatory cytokines that Th1 cells produce, such as interferon gamma, tumor necrosis factor-α, and interleukin-2, provide amplification and perpetuation of intestinal mucosal inflammation. Although the antigenic stimuli initiating the chronic T-cell mucosal immune response and inflammation are not completely delineated, increasing evidence supports the hypothesis that common intestinal bacteria induce the upregulated T-cell response due to genetically determined factors. The final destructive effector mechanisms continue to center on macrophages and granulocytes as well as the inflammatory mediators that they produce. Chemokines, proinflammatory cytokines, nitric oxide, and IgG plus complement continue to be shown as important mediators of chronic inflammatory injury to the intestine. Finally, the importance of healing processes mediated by growth factors within the intestine is receiving increasing attention.