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针对细胞因子治疗哮喘和慢性阻塞性肺疾病。

Targeting cytokines to treat asthma and chronic obstructive pulmonary disease.

机构信息

Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK.

出版信息

Nat Rev Immunol. 2018 Jul;18(7):454-466. doi: 10.1038/s41577-018-0006-6.

Abstract

Cytokines play a key role in orchestrating and perpetuating the chronic airway inflammation in asthma and chronic obstructive pulmonary disease (COPD), making them attractive targets for treating these disorders. Asthma and some cases of COPD are mainly driven by type 2 immune responses, which comprise increased airway eosinophils, T helper 2 (T2) cells and group 2 innate lymphoid cells (ILC2s) and the secretion of IL-4, IL-5 and IL-13. Clinical trials of antibodies that block these interleukins have shown reduced acute exacerbations and oral corticosteroid use and improvements in lung function and symptoms in selected patients. More recent approaches that block upstream cytokines, such as thymic stromal lymphopoietin (TSLP), show promise in improving patient outcome. Importantly, the clinical trials in cytokine blockade have highlighted the crucial importance of patient selection for the successful use of these expensive therapies and the need for biomarkers to better predict drug responses.

摘要

细胞因子在哮喘和慢性阻塞性肺疾病(COPD)的慢性气道炎症的发生和持续中起着关键作用,使它们成为治疗这些疾病的有吸引力的靶点。哮喘和一些 COPD 病例主要由 2 型免疫反应驱动,包括气道嗜酸性粒细胞、辅助性 T 细胞 2(T2)细胞和 2 型固有淋巴细胞(ILC2)增加,以及白细胞介素 4(IL-4)、白细胞介素 5(IL-5)和白细胞介素 13(IL-13)的分泌。阻断这些白细胞介素的抗体的临床试验表明,在选定的患者中,急性加重和口服皮质类固醇的使用减少,肺功能和症状得到改善。最近阻断上游细胞因子(如胸腺基质淋巴细胞生成素(TSLP))的方法显示出改善患者预后的希望。重要的是,细胞因子阻断的临床试验强调了为成功使用这些昂贵的治疗方法进行患者选择的至关重要性,以及需要生物标志物来更好地预测药物反应。

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