1. ¹Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, New Brunswick, New Jersey, USA
2. ²Tufts-New England Medical Center, Boston, Massachusetts, USA

Correspondence: Dr Alice B. Gottlieb, Tufts-New England Medical Center, 750 Washington St, Box 114, Boston, Massachusetts 02111, USA. E-mail: agottlieb@tufts-nemc.org

Received 25 August 2006; Revised 4 December 2006; Accepted 7 December 2006.

Abstract

Psoriasis is a chronic inflammatory disease of the skin affecting up to 2.5% of the world's population. The scaly, erythematous plaques characteristic of this papulosquamous disorder are likely triggered and maintained by cytokines and chemokines manufactured by cells of the immune system. Overproduction of inflammatory mediators, such as tumor necrosis factor-alpha (TNF-) and IFN-, results in a self-sustaining inflammatory cascade, causing abnormal keratinocyte proliferation and differentiation. Therapeutic drug design targeting TNF has led to the emergence of successful biologic agents, such as etanercept, in recent years. Despite extensive clinical trials documenting efficacious clinical response to therapy, there is a paucity of data investigating the molecular mechanisms by which etanercept modulates the improvement of psoriasis. This brief review summarizes recent work investigating the in vivo actions of etanercept, including its effects on various cell types, inflammatory pathways, gene activation, nuclear factor kappa B expression, and apoptosis. The anti-inflammatory properties of etanercept reveal mechanisms by which a TNF blockade may result in the improvement of psoriasis.