Human β‐defensin‐2 suppresses key features of asthma in murine models of allergic airways disease. Issue 1 (11th November 2020)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Clinical & experimental allergy. Volume 51:Issue 1(2021)
• Page Start: 120
• Page End: 131
• Publication Date: 2020-11-11
• Subjects: asthma -- steroid sensitive -- steroid resistant -- human β‐defensin‐2; Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.13766
• Languages: English
• ISSNs: 0954-7894

Abstract

Abstract: Background: 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. Objective: To elucidate the therapeutic potential of human β‐defensins (hBD), such as hBD2 mild to moderate and severe asthma. Methods: 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. Results: 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. Conclusions and Clinical relevance: These data indicate that hBD2 reduces the hallmark features and has potential as a new therapeutic agent in allergic and especially steroid‐resistant asthma.