Thomas Belinda J, Porritt Rebecca A, Hertzog Paul J, Bardin Philip G, Tate Michelle D
1] Monash Lung and Sleep, Monash Medical Centre, Clayton, Victoria, 3168, Australia [2] Centre for Innate Immunity and Infectious Diseases, MIMR-PHI Institute of Medical Research, Clayton, Victoria, 3168, Australia [3] Monash University, Clayton, Victoria, 3168, Australia.
1] Centre for Innate Immunity and Infectious Diseases, MIMR-PHI Institute of Medical Research, Clayton, Victoria, 3168, Australia [2] Monash University, Clayton, Victoria, 3168, Australia.
Sci Rep. 2014 Nov 24;4:7176. doi: 10.1038/srep07176.
Glucocorticosteroids (GCS) are used on a daily basis to reduce airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). This treatment is usually escalated during acute disease exacerbations, events often associated with virus infections. We examined the impact of GCS on anti-viral defences and virus replication and assessed supplementary interferon (IFN) treatment. Here, we report that treatment of primary human airway cells in vitro with GCS prior to rhinovirus (RV) or influenza A virus (IAV) infection significantly reduces the expression of innate anti-viral genes and increases viral replication. Mice given intranasal treatment with GCS prior to IAV infection developed more severe disease associated with amplified virus replication and elevated inflammation in the airways. Adjuvant IFN treatment markedly reduced GCS-amplified infections in human airway cells and in mouse lung. This study demonstrates that GCS cause an extrinsic compromise in anti-viral defences, enhancing respiratory virus infections and provides a rationale for adjuvant IFN treatment.
糖皮质激素（GCS）每日用于减轻哮喘和慢性阻塞性肺疾病（COPD）中的气道炎症。在急性疾病加重期（这些事件通常与病毒感染相关），这种治疗通常会加强。我们研究了GCS对抗病毒防御和病毒复制的影响，并评估了补充干扰素（IFN）治疗。在此，我们报告，在鼻病毒（RV）或甲型流感病毒（IAV）感染之前，用GCS体外处理原代人气道细胞会显著降低先天性抗病毒基因的表达并增加病毒复制。在IAV感染之前经鼻内给予GCS治疗的小鼠发生了更严重的疾病，这与病毒复制增加和气道炎症加剧有关。辅助性IFN治疗显著降低了人气道细胞和小鼠肺中GCS放大的感染。这项研究表明，GCS会导致抗病毒防御的外在损害，增强呼吸道病毒感染，并为辅助性IFN治疗提供了理论依据。
