TNf-Alpha and Apoptosis: Implications for the Pathogenesis and Treatment of Psoriasis
December 2002 | Volume 1 | Issue 3 | Original Article | 264 | Copyright © December 2002
Frank C. Victor, Alice B. Gottlieb
TNF-alpha is a key cytokine in innate immune responses and is increased in psoriatic lesions. TNF-alpha has
many effects, ranging from inflammation to apoptosis. These effects are reviewed to better understand the role
of TNF-alpha as it relates to the pathogenesis and treatment of psoriasis. TNF-alpha increases production of
pro-inflammatory molecules (e.g. IL-1, IL-6, IL-8, NF-kappaB, vasoactive intestinal peptide) and adhesion molecules
(e.g. intercellular adhesion molecule-1, P-selectin, E-selectin). TNF-alpha promotes apoptosis through
binding to the TNF-receptor 1; however, psoriatic lesions are hyperproliferative despite an increase in TNFalpha.
This paradox is partially explained as NF-kappaB activation seems to inhibit TNF-alpha-induced apoptosis.
The importance of TNF-alpha and apoptosis in psoriasis is shown through the review of clinical trials
using anti-TNF-alpha immunobiologics (e.g. etanercept, infliximab) and apoptosis-inducing treatments that
result in clinical improvement of the disease.