Rahmawati Siti Farah, Te Velde Maurice, Kerstjens Huib A M, Dömling Alexander S S, Groves Matthew Robert, Gosens Reinoud
Department of Molecular Pharmacology, University of Groningen, Groningen, Netherlands.
Department of Pharmacology and Clinical Pharmacy, Institut Teknologi Bandung, Bandung, Indonesia.
Front Allergy. 2021 Aug 30;2:694514. doi: 10.3389/falgy.2021.694514. eCollection 2021.
Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.
哮喘是一种呼吸系统疾病，目前全球约有3亿人受其影响，其特征为咳嗽、呼吸急促、喘息、黏液分泌过多、胸部发紧以及呼气气流受限。与健康对照相比，在哮喘患者的痰液、鼻和支气管活检组织以及血清中观察到白细胞介素17（IL-17）水平升高。IL-17水平较高的患者具有更严重的哮喘表型。生物制剂可用于治疗2型辅助性T细胞（Th2）水平高的哮喘患者，但Th17水平高的亚群对这些治疗的反应相对较低，使其成为一种较难治疗的严重哮喘表型。一些实验模型表明，靶向IL-17信号通路可能对哮喘有益。此外，由于Th17/IL-17轴的激活增加与吸入性糖皮质激素（ICS）敏感性降低相关，靶向IL-17信号通路可能会逆转ICS无反应性。在这篇综述中，我们介绍并讨论了目前关于IL-17在哮喘中的作用及其与Th2信号通路相互作用的知识，重点关注靶向IL-17信号通路的治疗原理。
