Lung irradiation increases mortality after influenza A virus challenge occurring late after exposure.

To address whether irradiation-induced changes in the lung environment alter responses to a viral challenge delivered late after exposure but before the appearance of late lung radiation injury.C57BL/6J mice received either lung alone or combined lung and whole-body irradiation (0-15 Gy). At 10 weeks after irradiation, animals were infected with 120 HAU influenza virus strain A/HKx31. Innate and adaptive immune cell recruitment was determined using flow cytometry. Cytokine and chemokine production and protein leakage into the lung after infection were assessed.Prior irradiation led to a dose-dependent failure to regain body weight after infection and exacerbated mortality, but it did not affect virus-specific immune responses or virus clearance. Surviving irradiated animals displayed a persistent increase in total protein in bronchoalveolar lavage fluid and edema.Lung irradiation increased susceptibility to death after infection with influenza virus and impaired the ability to complete recovery. This altered response does not seem to be due to a radiation effect on the immune response, but it may possibly be an effect on epithelial repair.