A Murine Model of Invasive Aspergillosis: Variable Benefit of Interferon-Gamma Administration under In Vitro and In Vivo Conditions

Publisher Website
Google Scholar
Abstract
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.

This publication has 41 references indexed in Scilit: