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

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-beta. We compared the mortality and innate immune responses of the treated mice following challenge with IAV. In NS mice, both early and late IFN-beta administration decreased the survival rate in mice infected with IAV, with late IFN-beta administration having the greatest effect on survival. In contrast, in CS-exposed mice, early IFN-beta administration significantly increased survival during IAV infection while late IFN-beta administration did not alter mortality. With regards to inflammation, in NS mice, IFN-beta administration, especially late administration, significantly increased IAV-induced inflammation and lung injury. Early IFN-beta administration to CS-exposed mice did not increase IAV-induced inflammation and lung injury as occurred in NS mice. Our results demonstrate, although IFN-beta administration worsens the susceptibility of NS mice to influenza infection with increased immunopathology, early IFN-beta administration to CS-exposed mice, which have suppression of the intrinsic IFN response, improved outcomes during influenza infection.

Automated summary

In smokers, early administration of IFN-beta can improve survival during influenza infection, while late administration does not alter mortality. In addition, IFN-beta treatment increases inflammation and lung injury induced by IAV infection, especially in nonsmokers.