Sci Rep . Early IFN-β administration protects cigarette smoke exposed mice against lethal influenza virus infection without increasing lung inflammation

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Sci Rep


. 2022 Mar 8;12(1):4080.
doi: 10.1038/s41598-022-08066-7.
Early IFN-β administration protects cigarette smoke exposed mice against lethal influenza virus infection without increasing lung inflammation


Wenxin Wu ¹ , Lili Tian ² , Wei Zhang ² , J Leland Booth ² , Jerry William Ritchey ³ , Shuhua Wu ⁴ , Chao Xu ⁵ , Brent R Brown ² , Jordan P Metcalf ^{6 7 8}



Affiliations

• PMID: 35260752
• DOI: 10.1038/s41598-022-08066-7

Free article

Abstract

During 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.