Author:
Wu Wenxin,Tian Lili,Zhang Wei,Booth J. Leland,Ritchey Jerry William,Wu Shuhua,Xu Chao,Brown Brent R.,Metcalf Jordan P.
Abstract
AbstractDuring influenza A virus (IAV) infection, it is unclear whether type I interferons (IFNs) have defensive antiviral effects or contribute to immunopathology in smokers. We treated nonsmoking (NS) and cigarette smoke (CS)-exposed mice intranasally with early (prophylactic) or late (therapeutic) IFN-β. We compared the mortality and innate immune responses of the treated mice following challenge with IAV. In NS mice, both early and late IFN-β administration decreased the survival rate in mice infected with IAV, with late IFN-β administration having the greatest effect on survival. In contrast, in CS-exposed mice, early IFN-β administration significantly increased survival during IAV infection while late IFN-β administration did not alter mortality. With regards to inflammation, in NS mice, IFN-β administration, especially late administration, significantly increased IAV-induced inflammation and lung injury. Early IFN-β administration to CS-exposed mice did not increase IAV-induced inflammation and lung injury as occurred in NS mice. Our results demonstrate, although IFN-β administration worsens the susceptibility of NS mice to influenza infection with increased immunopathology, early IFN-β administration to CS-exposed mice, which have suppression of the intrinsic IFN response, improved outcomes during influenza infection.
Funder
National Institute of General Medical Sciences
U.S. Department of Veterans Affairs
Publisher
Springer Science and Business Media LLC
Cited by
5 articles.
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