慢性呼吸道疾病中的白细胞介素-33：从临床前研究到临床研究
IL-33 in Chronic Respiratory Disease: From Preclinical to Clinical Studies.
作者信息
Donovan Chantal, Hansbro Philip M
机构信息
Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, Sydney, New South Wales 2050, Australia.
Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales 2308, Australia.
出版信息
ACS Pharmacol Transl Sci. 2019 Dec 20;3(1):56-62. doi: 10.1021/acsptsci.9b00099. eCollection 2020 Feb 14.
IL-33 has been deorphanized as a member of the IL-1 family and has key roles as an alarmin and cytokine with potent capacity to drive type 2 inflammation. This has led to a plethora of studies surrounding its role in chronic diseases with a type 2 inflammatory component. Here, we review the roles of IL-33 in two chronic respiratory diseases, asthma and chronic obstructive pulmonary disease (COPD). We discuss the hallmark and paradigm-shifting studies that have contributed to our understanding of IL-33 biology. We cover animal studies that have elucidated the mechanisms of IL-33 and assessed the role of anti-IL-33 treatment and immunization against IL-33. We highlight key clinical evidence for the potential of targeting increased IL-33 in respiratory diseases including exacerbations, and we outline current clinical trials using an anti-IL-33 monoclonal antibody in asthma patients. Finally, we discuss some of the challenges that have arisen in IL-33 biology and highlight potential future directions in targeting this cytokine in chronic respiratory diseases.
白细胞介素-33（IL-33）已被确定为白细胞介素-1家族的成员，作为一种警报素和细胞因子，具有驱动2型炎症的强大能力，发挥着关键作用。这引发了大量关于其在具有2型炎症成分的慢性疾病中作用的研究。在此，我们综述IL-33在两种慢性呼吸道疾病——哮喘和慢性阻塞性肺疾病（COPD）中的作用。我们讨论了有助于我们理解IL-33生物学特性的标志性和范式转变研究。我们涵盖了阐明IL-33机制、评估抗IL-33治疗及针对IL-33免疫作用的动物研究。我们强调了针对呼吸道疾病中升高的IL-33（包括病情加重）进行靶向治疗潜力的关键临床证据，并概述了目前在哮喘患者中使用抗IL-33单克隆抗体的临床试验。最后，我们讨论了IL-33生物学中出现的一些挑战，并强调了在慢性呼吸道疾病中靶向这种细胞因子的潜在未来方向。
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