Interleukin-18 Impairs the Pulmonary Host Response toPseudomonas aeruginosa

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Abstract
Interleukin-18 (IL-18) is a potent cytokine with many different proinflammatory activities. To study the role of IL-18 in the pathogenesis ofPseudomonaspneumonia, IL-18-deficient (IL-18−/−) and wild-type mice were intranasally inoculated withPseudomonasaeruginosa. IL-18 deficiency was associated with reduced outgrowth ofPseudomonasin 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 inIL-18−/−mice. Consistent with results obtained forIL-18−/−mice, treatment of wild-type mice with a neutralizing IL-18 binding protein-immunoglobulin G Fc fusion construct also attenuated outgrowth ofPseudomonascompared 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 duringPseudomonaspneumonia, concurrently impairing bacterial clearance.