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Infection and Immunity, October 2003, p. 5488-5497, Vol. 71, No. 10
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.10.5488-5497.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Interleukin-18 Facilitates the Early Antimicrobial Host Response to Escherichia coli Peritonitis

Sebastiaan Weijer,1,2* Miguel E. Sewnath,3 Alex F. de Vos,1 Sandrine Florquin,4 Koen van der Sluis,1 Dirk J. Gouma,3 Kiyoshi Takeda,5 Shizuo Akira,5 and Tom van der Poll1,2

Laboratory of Experimental Internal Medicine,1 Department of Infectious Diseases, Tropical Medicine and AIDS ,2 Department of Surgery,3 Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands,4 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan5

Received 19 March 2003/ Returned for modification 7 May 2003/ Accepted 13 July 2003

To determine the role of endogenous interleukin-18 (IL-18) during peritonitis, IL-18 gene-deficient (IL-18 KO) mice and wild-type mice were intraperitoneally (i.p.) infected with Escherichia coli, the most common causative agent found in septic peritonitis. Peritonitis was associated with a bacterial dose-dependent increase in IL-18 concentrations in peritoneal fluid and plasma. After infection, IL-18 KO mice had significantly more bacteria in the peritoneal lavage fluid and were more susceptible for progression to systemic infection at 6 and 20 h postinoculation than wild-type mice. The relative inability of IL-18 KO mice to clear E. coli from the abdominal cavity was not due to an intrinsic defect in the phagocytosing capacity of their peritoneal macrophages or neutrophils. IL-18 KO mice displayed an increased neutrophil influx into the peritoneal cavity, but these migratory neutrophils were less activate, as reflected by a reduced CD11b surface expression. These data suggest that endogenous IL-18 plays an important role in the early antibacterial host response during E. coli-induced peritonitis.

* Corresponding author. Mailing address: Department of Experimental Internal Medicine, Academic Medical Center Amsterdam, Meibergdreef 9, Room L0185, 1105 AZ Amsterdam, The Netherlands. Phone: 31205666034. Fax: 31206977192. E-mail: s.weijer{at}amc.uva.nl.

Editor: J. D. Clements

Infection and Immunity, October 2003, p. 5488-5497, Vol. 71, No. 10
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.10.5488-5497.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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