Cell Adhesion Molecules: Therapeutic Targets for Inhibition of Inflammatory States

The diversity of integrins and their complex role in many diseases suggests great potential for this superfamily as drug targets. The initial successes of anti-integrin therapeutics in the treatment of thrombotic disorders suggested that similar anti-integrin agents could be developed for the treatment of inflammatory disorders. While initially a promising strategy, inhibition of the integrins proved to be elusive despite the discovery of highly potent inhibitors. This is due to several reasons, including redundancy among the integrins and the importance of integrins in key physiological systems. Further exploration of the selective role for distinct leukocytic integrins indicated that homing of inflammatory cells to select disease sites depends on a highly regulated expression of discrete integrins and their ligands in limited locations. Selective control of integrin function is also regulated by local chemokines permitting exquisite homing of populations of inflammatory cells to disease sites. A more complete understanding of the regulation of integrin activation in disease states will permit the development of more effective and specific anti-integrin therapeutic agents.