1. Mechanisms of action of etanercept in psoriasis.
- Author
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Tan JK, Aphale A, Malaviya R, Sun Y, and Gottlieb AB
- Subjects
- Anti-Inflammatory Agents, Non-Steroidal adverse effects, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Apoptosis drug effects, Dendritic Cells drug effects, Dendritic Cells immunology, Down-Regulation drug effects, Etanercept, Humans, Immunoglobulin G adverse effects, Immunoglobulin G therapeutic use, Inflammation Mediators antagonists & inhibitors, Inflammation Mediators metabolism, NF-kappa B metabolism, Psoriasis genetics, Psoriasis immunology, Psoriasis pathology, Receptors, Tumor Necrosis Factor therapeutic use, Safety, T-Lymphocytes drug effects, T-Lymphocytes immunology, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha physiology, Immunoglobulin G pharmacology, Psoriasis drug therapy
- 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-alpha) and IFN-gamma, 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.
- Published
- 2007
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