New research on mice shows that pulmonary administration of granulocyte macrophage-colony stimulating factor (GM-CSF) significantly reduces flu symptoms and prevents death after a lethal dose of the influenza virus. Although GM-SCF therapy for humans as a flu prophylaxis or treatment is likely years away, the researchers find the results of the study, published in the American Journal of Respiratory and Critical Care, striking, as all the mice treated with GM-SCF survived after being infected with the influenza virus, whereas all untreated mice died from the same infection.
GM-SCF boosts innate immunity to make it immediately effective against the virus, and its protective effect has not been shown to be strain dependent so far. Alveolar macrophages (AM), which are enhanced by GM-SCF, are an essential piece of the innate immune response and are known to contribute to host defense against flu infections in animal models.
“Unlike a vaccine, GM-SCF 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 Homayoun Shams, PhD, principle study investigator from the University of Texas Health Science Center at Tyler.
The researchers set out to test the idea that boosting AM by introducing GM-SCF would protect against flu. They used three types of mice to test their hypothesis: wild-type (WT) mice, transgenic mice that do not express any GM-SCF (GM-/-), and transgenic mice that express GM-SCF only in the lung (SPC-GM). They infected all three strains of mice with lethal doses of influenza virus. After progressive weight loss, all WT and GM-/- mice died within days. In contrast, all SPC-GM mice survived, and they gained back the weight they initially lost after a short period.
“This proves the concept that GM-SCF, only in the lung, is sufficient to provide complete protection against infection with otherwise lethal doses of influenza virus strains, said Shams. “This finding delineates a novel means of conferring marked resistance to influenza through enhancing innate immune mechanisms that depend on AM. We found that SPC-GM mice that overexpress GM-SCF only in the lungs are highly resistant to infection with laboratory and clinical influenza strains, including the recent pandemic swine H1N1 strain.”
GM-SCF is already in use in humans as a therapy for neutropenia.
Source: American Journal of Respiratory and Critical Care Medicine