New Concepts of Pathogenesis in Inflammatory Bowel Disease

The precise etiology and mechanisms of inflammatory bowel disease (IBD) are still unclear. Nevertheless, several concepts are gaining acceptance and constitute the basis for a better understanding of its pathogenesis and for improved therapy. The association of Crohn’s disease (CD) and ulcerative colitis (UC) with ‘western’ lifestyle is well recognized, and is considered a reason for the increasing frequency of CD and UC in countries with previously low incidence. Proposed linkages of CD and UC with particular human leukocyte antigen haplotypes suggest a genetic predisposition, but no uniform or consistent patterns have emerged. Similarly, the study of susceptibility or disease markers has not offered reproducible results. The search for specific infectious agents is being pursued, and the measles virus is presently considered a possible culprit. A true explosion has occurred in the area of animal models, and a large number of chemically or genetically induced experimental colitides are at hand. Immunological factors continue to dominate the bulk of basic research in IBD. This area is vast and complex, and autoantibodies, immune, epithelial and mesenchymal cells, lipid mediators, cytokines, neuropeptides and oxygen metabolites are under investigation. Finally, other factors whose role in IBD is uncertain, including smoking and possible abnormalities of intestinal permeability or mucus composition, continue to receive attention. These extensive and varied efforts are yielding some profits, and new forms of therapy are being devised. Based mostly on studies of soluble mediators, a number of novel immunosuppressive and highly specific blocking agents are being developed and undergoing clinical trials