Interleukin-18 impairs the pulmonary host response to Pseudomonas aeruginosa.
Interleukin-18 (IL-18) is a potent cytokine with many different proinflammatory activities. To study the role of IL-18 in the pathogenesis of Pseudomonas pneumonia, IL-18-deficient (IL-18(-/-)) and wild-type mice were intranasally inoculated with Pseudomonas aeruginosa. IL-18 deficiency was associated with reduced outgrowth of Pseudomonas in the lungs and diminished dissemination of the infection. In addition, pulmonary inflammation (histopathology) and levels of tumor necrosis factor alpha, IL-6, and macrophage inflammatory protein-2 in lungs and plasma were lower in IL-18(-/-) mice. Consistent with results obtained for IL-18(-/-) mice, treatment of wild-type mice with a neutralizing IL-18 binding protein-immunoglobulin G Fc fusion construct also attenuated outgrowth of Pseudomonas compared with that for mice treated with a control protein. These results demonstrate that the presence of endogenous IL-18 activity facilitates inflammatory responses in the lung during Pseudomonas pneumonia, concurrently impairing bacterial clearance.
Schultz
Marc J
MJ
Laboratory of Experimental Internal Medicine, Department of Intensive Care Medicine, C3-326, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. m.j.schultz@amc.uva.nl
Knapp
Sylvia
S
Florquin
Sandrine
S
Pater
Jennie
J
Takeda
Kiyoshi
K
Akira
Shizuo
S
van der Poll
Tom
T
D000818:Animals; D016207:Cytokines / Q000097:blood; D005260:Female; D020382:Interleukin-18 / Q000502:physiology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology*
D016207:Cytokines; D020382:Interleukin-18