Background: Interferon-γ modulates host defense in a number of infectious diseases. Previous
studies have shown that systemic administration of interferon-gamma (IFN-γ) can enhance
survival in experimental invasive aspergillosis (IA).
Methods: Using a novel model of murine IA that is characterized by primary pulmonary
infection, we investigated the role of IFN-γ in the phagocytosis and killing of Aspergillus fumigatus
by murine neutrophils and pulmonary alveolar macrophages in vitro and the impact
of systemic and regional administration of IFN-γ on the course of IA in glucocorticoid-treated
mice.
Results: In vitro, IFN-γ significantly enhanced phagocytosis and killing function of both
neutrophils and alveolar macrophages from normal animals, but not cortisone-treated animals.
In vivo, intravenous administration of IFN-γ did not improve phagocyte recruitment,
in vivo killing, or mortality from IA. Regional (intranasal) administration of IFN-γ to the
lungs enhanced recruitment of phagocytic cells to the lungs and improved in vivo killing, but
did not alter (and actually worsened) mortality from IA.
Conclusions: The in vitro and in vivo effects of IFN-γ in IA are contingent on many variables,
including the route of administration and the specific pathogenesis of infection.
