Granulocyte Macrophage-Colony Stimulating Factor Protects Mice from the Flu

A study conducted on several different populations of mice found that that pulmonary administration of granulocyte macrophage-colony stimulating factor (GM-CSF) significantly reduced flu symptoms and prevented death after challenge with a lethal dose influenza virus.

GM-CSF protein is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. Alveolar macrophages (AM), which are enhanced by GM-CSF, are essential to the innate immune response and have been shown to contribute to host defense against flu infections in various animal models.

In the current study, investigators at the University of Texas Health Science Center (Tyler, USA) worked with three groups of mice: a normal wild type control group, a line that had been genetically engineered to lack the gene for GM-CSF, and a line that had the GM-CSF gene in one lung only. Animals from each group were infected with influenza virus in an initial series of experiments.

Results published in the April 7, 2011, online edition of the American Journal of Respiratory and Critical Care Medicine revealed that after progressive weight loss, all the wild type and GM-CSF null mice died within days. In contrast, all the mice carrying the GM-CSF gene survived, and these animals gained back the weight they had initially lost after a short period of time. The resistance of the transgenic mice to influenza was canceled by elimination of alveolar macrophages, but not by depletion of T-cells, B-cells, or neutrophils.

In a second series of experiments, animals were given GM-CSF after having been infected with the flu virus. Delivery of intranasal GM-CSF to the wild type mice conferred resistance to influenza to these animals. This resistance was apparently due to the enhancement of innate immune mechanisms that depend on alveolar macrophages.

"Such unique and unambiguous results demonstrate the great potential of GM-CSF and may be the remedy for a critical public health priority: developing strategies to reduce the morbidity and mortality from influenza,” said senior author Dr. Homayoun Shams, professor of pulmonary and infectious diseases at the University of Texas Health Science Center. "Improved methods to protect against influenza are sorely needed, particularly in the face of an impending pandemic. Development of such methods hinges on understanding host mechanisms that confer robust protection against influenza. Despite the widespread use of vaccines, influenza causes significant morbidity and mortality throughout the world, and those with poor immune systems are particularly more susceptible—such as very young, elderly, or immunocompromised individuals.”

"Unlike a vaccine, GM-CSF does not rely heavily on the body's ability to mount an immune counter-attack against a specific antigen or virus strain, but enhances the speed of local responses to virus infection and delicately balances the host immune responses," said Dr. Shams.

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University of Texas Health Science Center