Inhibition of LFA-1/ICAM-1 Interaction:A Therapeutic Strategy for Surmounting Inflammation

Leukocyte function associated antigen-1 (LFA-1, CD11a/CD18, αLβ₂) is a cell surface adhesion protein expressed on leukocytes. Interaction of LFA-1 with its counter receptor intercellular adhesion molecule-1 (ICAM-1) promotes the migration of leukocytes to the site of inflammation and is responsible for a variety of cell adhesion events required for normal and pathological functions of the immune system. Thus, the LFA-1/ICAM-1 interaction is thought to play a role in the pathogenesis of inflammatory and auto-immune disease conditions such as psoriasis, multiple sclerosis, asthma, rheumatoid arthritis, inflammatory bowel disease and transplant rejection. LFA-1/ICAM-1 interaction inhibitors have been extensively studied as a therapeutic target for clinically important diseases; leading to the development of therapeutic antibodies, peptides, peptidomimetics, allosteric and competitive inhibitors. However, despite of promising preclinical results, the outcome of clinical trials with LFA-1/ICAM-1 interaction inhibitors has been inconsistent and met with limited clinical success. This article gives a brief account of rationale and efficacy of different LFA-1/ICAM-1interaction inhibitors as promising therapeutic strategy for surmounting inflammatory disorders.