title: GM-CSF in the lung protects against lethal influenza infection.
abstract: BACKGROUND
  Alveolar macrophages contribute to host defenses against influenza in animal models. Enhancing alveolar macrophage function may contribute to protection against influenza.
  
  
  OBJECTIVE
  To determine if increased expression of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the lung increases resistance to influenza.
  
  
  METHODS
  Wild-type mice and transgenic mice that expressed GM-CSF in the lung were infected with influenza virus, and lung pathology, weight loss, and mortality were measured. We also administered GM-CSF to the lungs of wild-type mice that were infected with influenza virus.
  
  
  RESULTS
  Wild-type mice all died after infection with different strains of influenza virus, but all transgenic mice expressing GM-CSF in the lungs survived. The latter also had greatly reduced weight loss and lung injury, and showed histologic evidence of a rapid host inflammatory response that controlled infection. The resistance of transgenic mice to influenza was abrogated by elimination of alveolar phagocytes, but not by depletion of T cells, B cells, or neutrophils. Transgenic mice had far more alveolar macrophages than did wild-type mice, and they were more resistant to influenza-induced apoptosis. Delivery of intranasal GM-CSF to wild-type mice also conferred resistance to influenza.
  
  
  CONCLUSIONS
  GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of this cytokine has the potential to reduce the morbidity and mortality due to influenza virus.
authors.affiliation: Center for Pulmonary and Infectious Disease Control, University of Texas Health Science Center at Tyler, Texas, USA.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Huang
authors.forename: Peter F
authors.initials: PF
authors.lastname: Barnes
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Ruben
authors.initials: R
authors.lastname: Donis
authors.forename: Zissis C
authors.initials: ZC
authors.lastname: Chroneos
authors.forename: Steven
authors.initials: S
authors.lastname: Idell
authors.forename: Timothy
authors.initials: T
authors.lastname: Allen
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Perez
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Whitsett
authors.forename: Kyri
authors.initials: K
authors.lastname: Dunussi-Joannopoulos
authors.forename: Homayoun
authors.initials: H
authors.lastname: Shams
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000494:pharmacology*; D008168:Lung / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control*; D015431:Weight Loss / Q000276:immunology
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor