Chemokines in inflammatory bowel diseases

Abstract

Uncontrolled activation of mucosal effector cells has been identified as the main pathogenic mechanism involved in the initiation and perpetuation of mucosal inflammation in inflammatory bowel diseases (IBD). The sustained activation of these cells leads to the aberrant production of various pro-inflammatory mediators, which co-ordinated action amplifies the inflammatory process. In this setting a network of tissue-specific chemoattractant cytokines (chemokines) and their corresponding receptors have been implicated as main contributors in the initiation and perpetuation of the inflammatory reaction in IBD. They are produced by a variety of inflammatory cells present in IBD lesions, as well as endothelial and epithelial cells. Chemokines not only control the multistep process of leukocyte adhesion to and migration across the endothelium, but also the release of lipid mediators and oxygen radicals from leukocytes, the modulation of tumorigenesis, release of matrix metalloproteinases and tissue fibrosis. Numerous data indicate that that intestinal chemokine expression is non-selectively up-regulated in IBD and correlates with disease activity. The development of selective inhibitors for chemokines or chemokine receptors, based on a more complete understanding of the immunopathogenic role of chemokines in intestinal inflammation, will be of great interest as potential novel therapeutic strategies in IBD.