Role of interferon gamma in the pathogenesis of primary respiratory syncytial virus infection in BALB/c mice

Immunologic mechanisms are thought to contribute to the pathogenesis of respiratory syncytial virus (RSV) bronchiolitis in humans. RSV-infected BALB/c mice exhibit tachypnea and signs of outflow obstruction, similar to symptoms in humans. Interferon gamma (IFN gamma) has been found to be the predominant cytokine produced in humans and mice with RSV infection. We therefore undertook this study to evaluate the role of IFN gamma in the development of respiratory illness in RSV-infected mice. BALB/c mice were infected with RSV, and lung function was assessed by plethysmography. Bronchoalveolar lavage (BAL) fluids were analyzed for the concentration of interferon gamma (IFN gamma) and the presence of inflammatory cells, and lung tissue sections were examined for histopathologic changes. The role of IFN gamma was further addressed in studies of IFN gamma knock-out mice (IFN gamma(-/-)) and of mice depleted of IFN gamma by in vivo administration of a neutralizing antibody. After infection, mice developed respiratory symptoms that were strongly associated with the number of inflammatory cells in BAL, as well as with the concentrations of IFN-gamma. Both IFN-gamma(-/-) mice and mice treated with anti-IFN gamma developed more extensive inflammation of the airways than control mice. However mice lacking IFN gamma exhibited less severe signs of airway obstruction. Together these data suggest a protective role of IFN gamma in RSV infection in terms of limiting viral replication and inflammatory responses but also a pathogenic role in causing airway obstruction. (C) 2000 Wiley-Liss, Inc.