Balato Anna, Scala Emanuele, Balato Nicola, Caiazzo Giuseppina, Di Caprio Roberta, Monfrecola Giuseppe, Raimondo Annunziata, Lembo Serena, Ayala Fabio
a Department of Advanced Biomedical Sciences , University of Naples Federico II , Naples , Italy.
b Department of Clinical Medicine and Surgery , University of Naples Federico II , Naples , Italy.
Expert Opin Biol Ther. 2017 Nov;17(11):1363-1374. doi: 10.1080/14712598.2017.1363884. Epub 2017 Aug 9.
Advances in the understanding of TNF-α and IL-17 synergistic functions have recently led to the concept that patients who do not respond or who respond inadequately to TNF-α inhibitors may have IL-17-driven diseases, opening up the way for a new class of therapeutic development: Th17-inhibitors. Areas covered: In this review, the authors discuss the central role that the IL-23/Th17 axis plays in the pathogenesis of several inflammatory diseases, such as psoriasis, highlighting its position as a relevant therapeutic target. In particular, the authors start by giving a brief historical excursus on biologic agent development up until the success of TNF-α inhibitors, and continue with an overview of IL12/23 pathway inhibition. Next, they describe Th17 cell biology, focusing on the role of IL-17 in host defense and in human immune-inflammatory diseases, discussing the use and side effects of IL-17 inhibitors. Expert opinion: The IL-23/Th17 signaling pathway plays a central role in the pathogenesis of several inflammatory diseases, such as psoriasis. Recent data has demonstrated that biologics neutralizing IL-17 (ixekizumab, secukinumab) or its receptor (brodalumab) are highly effective with a positive safety profile in treating moderate to severe psoriasis, offering new treatment possibilities, especially for patients who do not respond adequately to anti-TNF-α therapies.
对肿瘤坏死因子-α（TNF-α）和白细胞介素-17（IL-17）协同功能认识的进展，近来引发了这样一种概念：对TNF-α抑制剂无反应或反应不充分的患者，可能患有IL-17驱动的疾病，这为一类新的治疗药物开发——Th17抑制剂开辟了道路。涵盖领域：在本综述中，作者讨论了IL-23/Th17轴在几种炎症性疾病（如银屑病）发病机制中所起的核心作用，强调了其作为一个相关治疗靶点的地位。具体而言，作者首先简要回顾了生物制剂的研发历程，直至TNF-α抑制剂取得成功，接着概述了IL12/23通路抑制。随后，他们描述了Th17细胞生物学，重点关注IL-17在宿主防御及人类免疫炎症性疾病中的作用，探讨了IL-17抑制剂的应用及副作用。专家观点：IL-23/Th17信号通路在几种炎症性疾病（如银屑病）的发病机制中起核心作用。最近的数据表明，中和IL-17（司库奇尤单抗、依奇珠单抗）或其受体（布罗达单抗）的生物制剂在治疗中度至重度银屑病方面具有高效性且安全性良好，提供了新的治疗选择，尤其是对于对抗TNF-α疗法反应不充分的患者。
