Etanercept suppresses regenerative hyperplasia in psoriasis by acutely downregulating epidermal expression of interleukin (IL)-19, IL-20 and IL-24

Br J Dermatol. 2012 Jul;167(1):92-102. doi: 10.1111/j.1365-2133.2012.10961.x.


Background: Psoriasis is a Th17/Th1-mediated skin disease that often responds to antitumour necrosis factor (TNF)-α therapies, such as etanercept.

Objectives: To better define mechanisms by which etanercept improves psoriasis and to gain insight into disease pathogenesis.

Methods: We investigated the early biochemical and cellular effects of etanercept on skin lesions in responder patients prior to substantial clinical improvement (≤ 4 weeks).

Results: By 1 week, etanercept acutely suppressed gene expression of the interleukin (IL)-20 subfamily of cytokines (IL-19, IL-20, IL-24), which were found to be predominantly epidermis-derived and which are implicated in stimulating epidermal hyperplasia. Additionally, by 1 week of therapy, suppression of other keratinocyte-derived products (chemokines, antimicrobial proteins) occurred, while suppression of epidermal regenerative hyperplasia occurred within 1-3 weeks. Th17 elements (IL-23p19, IL-12p40, IL-17A, IL-22) were suppressed by 3-4 weeks. In vitro, TNF-α and IL-17A coordinately stimulated the expression of the IL-20 subfamily in normal keratinocytes.

Conclusions: Based on the rapid suppression of regenerative hyperplasia, chemokines and other keratinocyte-derived products, including the IL-20 subfamily, we propose that epidermal activation is a very early target of etanercept. As many of these keratinocyte markers are stimulated by TNF-α, their rapid downregulation is likely to reflect etanercept's antagonism of TNF-α. Additionally, decreased epidermal hyperplasia might result specifically from acute suppression of the IL-20 subfamily, which is also a likely consequence of etanercept's antagonism of TNF-α. Thus, the IL-20 subfamily has potential importance in the pathogenesis of psoriasis and therapeutic response to etanercept.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Dendritic Cells / physiology
  • Down-Regulation
  • Epidermis / metabolism
  • Epidermis / pathology*
  • Epidermis / physiology
  • Etanercept
  • Humans
  • Hyperplasia / metabolism
  • Immunoglobulin G / therapeutic use*
  • Interleukins / metabolism*
  • Keratinocytes / physiology
  • Lymphocyte Activation / physiology
  • Middle Aged
  • Psoriasis / drug therapy*
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Regeneration / physiology
  • T-Lymphocytes / physiology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / physiology
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • Immunoglobulin G
  • Interleukins
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept