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

摘要: Summary 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 gain insight into pathogenesis. Methods  We investigated the early biochemical cellular effects of on lesions in responder patients prior substantial clinical improvement (≤ 4 weeks). Results  By 1 week, acutely suppressed gene expression interleukin (IL)-20 subfamily cytokines (IL-19, IL-20, IL-24), were found be predominantly epidermis-derived are implicated stimulating epidermal hyperplasia. Additionally, 1 week therapy, suppression other keratinocyte-derived products (chemokines, antimicrobial proteins) occurred, while regenerative hyperplasia occurred within 1–3 weeks. Th17 elements (IL-23p19, IL-12p40, IL-17A, IL-22) 3–4 weeks. In vitro, TNF-α IL-17A coordinately stimulated IL-20 normal keratinocytes. Conclusions  Based rapid hyperplasia, chemokines products, including subfamily, we propose activation very target etanercept. As many these keratinocyte markers TNF-α, their downregulation likely reflect etanercept’s antagonism TNF-α. decreased might result specifically from acute also consequence Thus, has potential importance pathogenesis therapeutic response