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We treated nonsmoking (NS) and cigarette smoke (CS)-exposed mice intranasally with early (prophylactic) or late (therapeutic) IFN-\u03b2. We compared the mortality and innate immune responses of the treated mice following challenge with IAV. In NS mice, both early and late IFN-\u03b2 administration decreased the survival rate in mice infected with IAV, with late IFN-\u03b2 administration having the greatest effect on survival. In contrast, in CS-exposed mice, early IFN-\u03b2 administration significantly increased survival during IAV infection while late IFN-\u03b2 administration did not alter mortality. With regards to inflammation, in NS mice, IFN-\u03b2 administration, especially late administration, significantly increased IAV-induced inflammation and lung injury. Early IFN-\u03b2 administration to CS-exposed mice did not increase IAV-induced inflammation and lung injury as occurred in NS mice. Our results demonstrate, although IFN-\u03b2 administration worsens the susceptibility of NS mice to influenza infection with increased immunopathology, early IFN-\u03b2 administration to CS-exposed mice, which have suppression of the intrinsic IFN response, improved outcomes during influenza infection.<\/jats:p>","DOI":"10.1038\/s41598-022-08066-7","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T13:02:36Z","timestamp":1646744556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Early IFN-\u03b2 administration protects cigarette smoke exposed mice against lethal influenza virus infection without increasing lung inflammation"],"prefix":"10.1038","volume":"12","author":[{"given":"Wenxin","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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