In the United States, influenza annually infects 5-20% of the
population, causes >200,000 hospitalizations and 40,000 deaths.
Avian H5N1 viruses are extremely virulent and cause pandemic
disease. The current H1N1 pandemic has caused significant
morbidity and mortality, and incurred major financial costs. The
human and economic burden of influenza mandates improved methods
of treatment and prevention. Our preliminary data show that
expression of granulocyte macrophage-colony stimulating factor
(GM-CSF) in the lung provides remarkable protection against
influenza A virus (IAV), and that resistance depends on alveolar
macrophages. The mortality of IAV infection in SPC-GM transgenic
mice that overexpress GM-CSF only in the lung was 0%, compared
to 100% in wild-type mice. Furthermore, pulmonary delivery of
GM-CSF to wild type mice abrogated mortality from IAV. Data on
how GM-CSF confers extraordinary resistance to IAV by enhancing
innate immune mechanisms will be presented and the potential of
GM-CSF to prevent an