Interleukin-18 impairs the pulmonary host response to Pseudomonas aeruginosa

Marc J. Schultz, Sylvia Knapp, Sandrine Florquin, Jennie Pater, Kiyoshi Takeda, Shizuo Akira, Tom van der Poll

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60 Citations (Scopus)

Abstract

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 Fe 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
Original languageEnglish
Pages (from-to)1630-1634
JournalInfection and immunity
Volume71
Issue number4
DOIs
Publication statusPublished - 2003

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