Leukocyte and endothelial cell adhesion molecules as targets for therapeutic interventions in inflammatory disease.

Inflammation is a fundamental response to tissue injury and invasion of pathogens, but it is detrimental in clinically important inflammatory disorders. Leukocytes are key players in the inflammatory response because of their antimicrobial, secretory and phagocytic activities. They are recruited to the inflamed tissue by sequential adhesive interactions between leukocytes and the endothelium that are mediated by cell-adhesion molecules (CAMs) on the surface of the interacting cells. The effects of many anti-inflammatory drugs can be ascribed, in part, to inhibition of the expression of CAMs. However, in the search for more selective and potent drugs for clinically important diseases such as multiple sclerosis, asthma, rheumatoid arthritis, inflammatory bowel disease, allergies and atherosclerosis, direct inhibition of the function of CAMs has attracted increasing interest. In recent years, the development of synthetic antagonists has provided better opportunities for drug targeting. Future advances in this field hold new prospects for therapeutic intervention in human inflammatory disorders.