Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL, 32306.
Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, 32306.
Med Res Rev. 2017 Jan;37(1):180-216. doi: 10.1002/med.21406. Epub 2016 Sep 8.
Inflammation plays a major role in the induction and progression of several skin diseases. Overexpression of the major epidermal proinflammatory cytokines interleukin (IL) 1 alpha (IL-1α) and 1 beta (IL-1β) is positively correlated with symptom exacerbation and disease progression in psoriasis, atopic dermatitis, neutrophilic dermatoses, skin phototoxicity, and skin cancer. IL-1β and the interleukin-1 receptor I (IL-1RI) have been used as a therapeutic target for some autoinflammatory skin diseases; yet, their system-wide effects limit their clinical usage. Based on the local effects of extracellular IL-1α and its precursor, pro-IL-1α, we hypothesize that this isoform is a promising drug target for the treatment and prevention of many skin diseases. This review provides an overview on IL-1α and IL-β functions, and their contribution to inflammatory and malignant skin diseases. We also discuss the current treatment regimens, and ongoing clinical trials, demonstrating the potential of targeting IL-1α, and not IL-1β, as a more effective strategy to prevent or treat the onset and progression of various skin diseases.
炎症在几种皮肤疾病的诱导和进展中起着重要作用。在银屑病、特应性皮炎、中性粒细胞皮肤病、皮肤光毒性和皮肤癌中，表皮主要促炎细胞因子白细胞介素 (IL) 1α (IL-1α) 和 1β (IL-1β) 的过度表达与症状加重和疾病进展呈正相关。IL-1β 和白细胞介素-1 受体 I (IL-1RI) 已被用作一些自身炎症性皮肤病的治疗靶点；然而，它们的全身作用限制了它们的临床应用。基于细胞外 IL-1α 和其前体 pro-IL-1α 的局部作用，我们假设这种同工型是治疗和预防许多皮肤疾病的有前途的药物靶点。这篇综述提供了对 IL-1α 和 IL-β 功能及其对炎症和恶性皮肤疾病的贡献的概述。我们还讨论了当前的治疗方案和正在进行的临床试验，证明靶向 IL-1α 而不是 IL-1β 作为预防或治疗各种皮肤疾病发作和进展的更有效策略的潜力。
