Delivering protein to lungs of mice protected against lethal challenge with multiple flu strains.
Researchers have shown that administering granulocyte macrophage-colony stimulating factor (GM-CSF) to the lungs of mice protects against infection with otherwise lethal doses of influenza virus including H1N1. The work, led by Homayoun Shams, Ph.D., at the Center for Pulmonary and Infectious Disease Control at the University of Texas Health Science Center, found that GM-CSF acts to boost the activity of alveolar macrophages rather than trigger B- or T cell-mediated mechanisms.
They hope to eventually carry out clinical trials to test whether pulmonary delivery of GM-CSF can also protect people against flu. Their studies in mice are reported in the American Journal of Respiratory and Critical Care Medicine in a paper titled “GM-CSF in the lung protects against lethal influenza infection.”
In their work, Dr. Shams team demonstrated that all wild-type mice died after infection with different strains of flu virus. In contrast, transgenic mice that overexpressed GM-CSF just in their lungs all survived after infection. Intranasal delivery of GM-CSF to the wild-type mice boosted their resistance to subsequent infection with flu, and all these animals also survived. Administering a GM-CSF-expressing plasmid to the lungs of wild-type mice similarly increased their resistance to challenge with influenza.
The GM-CSF expressing mice were found to have more AM than wild-type mice and were more resistant to influenza-induced apoptosis. These animals in addition demonstrated markedly reduced lung injury and alveolar damage after infection with influenza virus along with increased baseline lung levels of MCP-1 and TNF-α and earlier histologic evidence of post-infection mononuclear cell infiltrates. The authors suggest this latter observation indicates the development of a more rapid host inflammatory response that reduced the viral burden.