Dual Inhibition of IL-12/IL-23 and Selective Inhibition of IL-23 in Psoriasis

Abstract

The etiology of psoriasis is unknown, although it is generally believed to be a complex T cell-mediated inflammatory disease with a genetic basis [1, 2]. CD4+ T helper cells, called T helper (Th) 17 cells, are important in the pathogenesis of psoriasis [2–5]. Interleukin (IL)-23 stimulates survival and proliferation of Th17 cells and thus serves as a key upstream cytokine regulator for this disease. Within psoriatic skin lesions, IL-23 is overproduced by activated dermal dendritic cells, and this in turn stimulates Th17 cells within the skin to survive and produce cytokines, including IL-17A. IL-17A and other pro-inflammatory cytokines drive keratinocyte activation and hyperproliferation in psoriasis. This review will focus on the role of IL-23 in psoriasis pathogenesis and the therapeutic targeting of IL-23 by monoclonal antibodies in patients with psoriasis.