Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Curr Opin Pulm Med. 2018 Jan;24(1):32-41. doi: 10.1097/MCP.0000000000000443.
Recent studies have highlighted the role of alarmins in asthma pathophysiology and tested the roles of these cytokines in asthmatic patients. This review will discuss the recent advances in the role of alarmins in asthma and the potential of future targeted therapies in asthma.
Epithelial-derived cytokines can be released upon exposure to external stimuli, causing damage to the epithelial barrier and resulting in tissue inflammation. Of these cytokines, IL-25, IL-33 and thymic stromal lymphopoeitin (TSLP), have been associated with asthma. These alarmins are all not only overexpressed in asthmatic airways, particularly in airway epithelial cells, but also in other structural and immune cells. Furthermore, all three alarmins drive type-2 pro-inflammatory responses in several immune cells that have been identified as key players in the pathogenesis of asthma, including innate lymphoid type-2 cells. Clinical trials testing therapeutics that block pathways of the alarmins are in progress.
To-date, only TSLP blockade has been reported in human clinical trials, and this approach has shown efficacy in asthmatic patients. Current body of evidence suggests that alarmins are useful upstream targets for treatment of asthma.
最近的研究强调了警报素在哮喘发病机制中的作用，并测试了这些细胞因子在哮喘患者中的作用。这篇综述将讨论警报素在哮喘中的作用的最新进展，以及哮喘未来靶向治疗的潜力。
上皮细胞衍生的细胞因子在暴露于外部刺激时可以释放，导致上皮屏障损伤，导致组织炎症。在这些细胞因子中，IL-25、IL-33 和胸腺基质淋巴生成素 (TSLP) 与哮喘有关。这些警报素不仅在哮喘气道中过度表达，特别是在气道上皮细胞中，而且在其他结构和免疫细胞中也过度表达。此外，所有三种警报素都在几种被认为是哮喘发病机制关键参与者的免疫细胞中驱动 2 型促炎反应，包括先天淋巴样细胞 2 型细胞。正在进行临床试验，以测试阻断警报素途径的治疗方法。
迄今为止，仅在人类临床试验中报道了 TSLP 阻断，这种方法已显示出对哮喘患者的疗效。目前的证据表明，警报素是治疗哮喘的有用上游靶点。
