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Infection and Immunity, April 2003, p. 1630-1634, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1630-1634.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Interleukin-18 Impairs the Pulmonary Host Response to Pseudomonas aeruginosa

Marc J. Schultz,1,2* Sylvia Knapp,1 Sandrine Florquin,3 Jennie Pater,1 Kiyoshi Takeda,4 Shizuo Akira,4 and Tom van der Poll1,5

Laboratory of Experimental Internal Medicine,1 Department of Intensive Care Medicine,2 Department of Pathology,3 Department of Infectious Diseases, Tropical Medicine, and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands,5 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan4

Received 21 June 2002/ Returned for modification 15 August 2002/ Accepted 3 January 2003

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.

* Corresponding author. Mailing address: Academic Medical Center, University of Amsterdam, Department of Intensive Care Medicine, C3-326, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Phone: 31-20-5669111. Fax: 31-20-5669568. E-mail: m.j.schultz{at}amc.uva.nl.

Editor: J. D. Clements

Infection and Immunity, April 2003, p. 1630-1634, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1630-1634.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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