GM-CSF in the lung protects against lethal influenza infection

http://www.ncbi.nlm.nih.gov/pubmed/21474645

Am J Respir Crit Care Med. 2011 Apr 7. [Epub ahead of print]

GM-CSF in the Lung Protects Against Lethal Influenza Infection.

Huang FF, Barnes PF, Feng Y, Donis R, Chroneos ZC, Idell S, Allen T, Perez DR, Whitsett JA, Dunussi-Joannopoulos K, Shams H.

Center for Pulmonary and Infectious Disease Control, University of Texas Health Science Center at Tyler, Tyler, Texas, United States.

Abstract
RATIONALE: 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 in the lung increases resistance to influenza

METHODS: Wild-type mice and transgenic mice that expressed granulocyte macrophage-colony stimulating factor in the lung were infected with influenza virus, and lung pathology, weight loss and mortality were measured. We also administered granulocyte-macrophage colony stimulating factor to the lungs of wild-type mice that were infected with influenza virus.

MEASUREMENTS AND MAIN RESULTS: Wild-type mice all died after infection with different strains of influenza virus, but all transgenic mice expressing granulocyte-macrophage colony stimulating factor 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 wild-type mice, and they were more resistant to influenza-induced apoptosis. Delivery of intranasal granulocyte macrophage-colony stimulating factor to wild-type mice also conferred resistance to influenza.

CONCLUSIONS: Granulocyte-macrophage colony stimulating factor 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.