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ABSTRACT: Rationale
Severe respiratory syncytial virus (RSV) bronchiolitis has been associated with deficient IFN-gamma production in humans, but the role of this cytokine in determining the outcome of reinfection is unknown.Objectives
To define the role of IFN-gamma in the development of RSV-mediated airway hyperresponsiveness (AHR) and lung histopathology in mice.Methods
Wild-type (WT) and IFN-gamma knockout mice were infected with RSV in the newborn or weaning stages and reinfected 5 weeks later. Airway responses were assessed on Day 6 after the primary or secondary infection.Measurements and main results
Both WT and IFN-gamma knockout mice developed similar levels of AHR and airway inflammation after primary infection. After reinfection, IFN-gamma knockout mice, but not WT mice, developed AHR, airway eosinophilia, and mucus hyperproduction. Intranasal administration of IFN-gamma during primary infection but not during reinfection prevented the development of these altered airway responses on reinfection in IFN-gamma knockout mice. Adoptive transfer of WT T cells into IFN-gamma knockout mice before primary infection restored IFN-gamma production in the lungs and prevented the development of altered airway responses on reinfection. Treatment of mice with IFN-gamma during primary neonatal infection prevented the enhancement of AHR and the development of airway eosinophilia and mucus hyperproduction on reinfection.Conclusions
IFN-gamma production during primary RSV infection is critical to the development of protection against AHR and lung histopathology on reinfection. Provision of IFN-gamma during primary infection in infancy may be a potential therapeutic approach to alter the course of RSV-mediated long-term sequelae.
SUBMITTER: Lee YM
PROVIDER: S-EPMC2204078 | biostudies-literature | 2008 Jan
REPOSITORIES: biostudies-literature
American journal of respiratory and critical care medicine 20071025 2
<h4>Rationale</h4>Severe respiratory syncytial virus (RSV) bronchiolitis has been associated with deficient IFN-gamma production in humans, but the role of this cytokine in determining the outcome of reinfection is unknown.<h4>Objectives</h4>To define the role of IFN-gamma in the development of RSV-mediated airway hyperresponsiveness (AHR) and lung histopathology in mice.<h4>Methods</h4>Wild-type (WT) and IFN-gamma knockout mice were infected with RSV in the newborn or weaning stages and reinfec ...[more]