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 various pathogens. To study the role of IFN-gamma in the pathogenesis of Pseudomonas pneumonia, IFN-gamma receptor (R) alpha-subunit-deficient [IFN-gammaR(-/-)] mice and wild type mice were intranasally inoculated with Pseudomonas aeruginosa (10(5) CFU). IFN-gammaR(-/-) mice demonstrated an enhanced clearance of P. aeruginosa from their lungs when compared to normal wild type mice (P < 0.05 at 24 hours after the infection), which was associated with a tendency towards an improved survival. These findings were not accompanied by a more effective activation of several components of the innate immune system known to contribute to host defense against pneumonia, i.e. the lung concentrations of cytokines and chemokines were similar in IFN-gammaR(-/-) and wild type mice, while the influx of neutrophils in bronchoalveolar lavage fluid (BALF) was even higher in wild type mice than in IFN-gammaR(-/-) mice. Remarkably, IFN-gammaR(-/-) mice had higher nitric oxide levels in the BALF at 24 hours after infection (P < 0.05). Endogenous IFN-gamma impairs rather than augments host defense during pneumonia caused by P. aeruginosa.
Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
M J
MJ
Schultz
A W
AW
Rijneveld
P
P
Speelman
S J
SJ
van Deventer
T
T
van der Poll
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*
D007371:Interferon-gamma