Pinkerton James W, Kim Richard Y, Koeninger Louis, Armbruster Nicole S, Hansbro Nicole G, Brown Alexandra C, Jayaraman Ranjith, Shen Sijie, Malek Nisar, Cooper Matthew A, Nordkild Peter, Horvat Jay C, Jensen Benjamin A H, Wehkamp Jan, Hansbro Philip M
Priority Research Centre for Healthy Lungs, University of Newcastle, & Hunter Medical Research Institute, Newcastle, NSW, Australia.
National Heart & Lung Institute, Imperial College London, London, UK.
Clin Exp Allergy. 2021 Jan;51(1):120-131. doi: 10.1111/cea.13766. Epub 2020 Nov 11.
Asthma is an airway inflammatory disease and a major health problem worldwide. Anti-inflammatory steroids and bronchodilators are the gold-standard therapy for asthma. However, they do not prevent the development of the disease, and critically, a subset of asthmatics are resistant to steroid therapy.
To elucidate the therapeutic potential of human β-defensins (hBD), such as hBD2 mild to moderate and severe asthma.
We investigated the role of hBD2 in a steroid-sensitive, house dust mite-induced allergic airways disease (AAD) model and a steroid-insensitive model combining ovalbumin-induced AAD with C muridarum (Cmu) respiratory infection.
In both models, we demonstrated that therapeutic intranasal application of hBD2 significantly reduced the influx of inflammatory cells into the bronchoalveolar lavage fluid. Furthermore, key type 2 asthma-related cytokines IL-9 and IL-13, as well as additional immunomodulating cytokines, were significantly decreased after administration of hBD2 in the steroid-sensitive model. The suppression of inflammation was associated with improvements in airway physiology and treatment also suppressed airway hyper-responsiveness (AHR) in terms of airway resistance and compliance to methacholine challenge.
These data indicate that hBD2 reduces the hallmark features and has potential as a new therapeutic agent in allergic and especially steroid-resistant asthma.
哮喘是一种气道炎症性疾病，是全球主要的健康问题。抗炎类固醇和支气管扩张剂是哮喘的金标准治疗方法。然而，它们并不能预防疾病的发展，而且至关重要的是，一部分哮喘患者对类固醇治疗有抗性。
阐明人β-防御素（hBD），如hBD2在轻度至中度和重度哮喘中的治疗潜力。
我们在类固醇敏感、屋尘螨诱导的过敏性气道疾病（AAD）模型以及将卵清蛋白诱导的AAD与鼠支原体（Cmu）呼吸道感染相结合的类固醇不敏感模型中研究了hBD2的作用。
在这两种模型中，我们均证明经鼻给予hBD2进行治疗可显著减少炎症细胞流入支气管肺泡灌洗液。此外，在类固醇敏感模型中给予hBD2后，关键的2型哮喘相关细胞因子IL-9和IL-13以及其他免疫调节细胞因子均显著降低。炎症的抑制与气道生理功能的改善相关，并且治疗在气道阻力和对乙酰甲胆碱激发试验的顺应性方面也抑制了气道高反应性（AHR）。
这些数据表明，hBD2可减轻标志性特征，在过敏性尤其是类固醇抗性哮喘中具有作为新型治疗药物的潜力。
