Endogenous interferon-gamma impairs bacterial clearance from lungs during Pseudomonas aeruginosa pneumonia

Interferon (IFN-)gamma is thought to play a role in the resistance to vario us pathogens. To study the role of IFN-gamma in the pathogenesis of Pseudom onas pneumonia, IFN-gamma receptor (R) alpha -subunit-deficient [IFN-gammaR ((-/-))] mice and wild type mice were intranasally inoculated with Pseudomo na aeruginosa (10(5) CFU), IFN-gammaR((-/-)) mice demonstrated an enhanced clearance of P. aeruginosa from their lungs when compared to normal wild ty pe mice (P < 0.05 at 24 hours after the infection), which was associated wi th a tendency towards an improved survival, These findings were not accompa nied by a more effective activation of several components of the innate imm une system known to contribute to host defense against pneumonia, i.e. the lung concentrations of cytokines and chemokines were similar in IFN-<gamma> R(-/-) and wild type mice, while the influx of neutrophils in bronchoalveol ar lavage fluid (BALF) was even higher in wild type mice than in IFN-gammaR ((-/-)) mice, Remarkably, IFN-gammaR((-/-)) mice had higher nitric oxide le vels in the BALF at 24 hours after infection (P < 0.05), Endogenous IFN-<ga mma> impairs rather than augments host defense during pneumonia caused by P . aeruginosa.