Lifitegrast, a Lymphocyte Function-Associated Antigen-1 Antagonist Demonstrates Beneficial Effect in Psoriasis

Abstract

Lifitegrast is a lymphocyte function-associated antigen-1 (LFA-1) antagonist, which is approved for treatment of dry eye disease. In this work we explored the effect of lifitegrast in imiquimod induced psoriasis model in mice. Lifitegrast (5% solution) was tested in imiquimod-induced psoriasis model in C57 mice. Lifitegrast was topically administered twice a day to the psoriatic skin for 6 days and epidermal skin thickness, psoriasis area and severity index (PASI) score and inflammation markers were assessed. Lifitegrast inhibited the imiquimod-induced increase in the epidermal thickness, histopathological changes and PASI score. This decrease in psoriasis inflammation was accompanied by decrease in TNF-α, IL-6, IL-22 and IL-17/IL-23 axis gene expression in the skin, and the effect is comparable to the oral cyclosporine A(5 mg/kg, twice a day) treatment. Lifitegrast demonstrated significant anti-inflammatory activity, mainly through reduction in cytokine gene expression related to psoriasis and decreased the severity of psoriasis in vivo. The significant effect shown by this LFA-1 and ICAM-1 antagonist indicates a novel topical treatment for psoriasis.