Advances have been made in understanding the biological processes underlying the chronic inflammatory pathways associated with the two primary forms of IBD, ulcerative colitis and Crohn’s disease. The uncontrolled inflammatory response to antigens in the gut is partly a result of an immune system dysfunction. This dysregulation may at least in part depend on an imbalance of mucosal inflammatory (Th1, Th2) cells and counter regulatory cells (Il-10, TGF–ß1, PGE2), leading to uncontrolled inflammation in the gut (1).
There is evidence that in IBD the cell-mediated arm of the adaptive immune system results in either an excessive T helper (Th1) immune response, which is associated with Crohn’s disease, or a T helper 2 (Th2) immune response, which is associates with ulcerative colitis (2). Despite the fact that these diseases exhibit different Th1/Th2 cytokine profiles, downstream inflammatory events may be the same and in both conditions, proinflammatory cytokines, such as TNF-alpha, are produced in excess (1).
Among these pro-inflammatory cytokines, TNF-alpha plays an important role in the inflammatory cascade of IBD and is thought to induce many other pro-inflammatory responses in the gut, including activation of macrophages that promote the release of other proinflammatory mediators, inducing expression of adhesion molecules which leads to an influx of new inflammatory cells into the mucosa. TNF-alpha can also alter the integrity of the epithelial membranes, thus contributing to the intestinal damage (1).
Abbott supports research efforts to elucidate the pathogenic mechanisms of IBD in order to develop biologic therapeutic agents that target specific pathways in the inflammatory cascade.
- Pallone F, Monteleone G, Monteleone I, Biancone L. The immune system in inflammatory bowel disease. In Satsangi J, Sutherland LR, eds. Inflammatory Bowel Diseases. London: Churchill Livingstone. Elsevier Limited, 2003: 85-93.
- Hanauer SB. Inflammatory Bowel Disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflammatory Bowel Disease 2006; 12: S3-S9.