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Infection and Immunity, February 1999, p. 478-483, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Interleukin 18 Contributes to Host Resistance and Gamma Interferon Production in Mice Infected with Virulent Salmonella typhimurium

Pietro Mastroeni,1,* S. Clare,1 S. Khan,2 J. A. Harrison,3 C. E. Hormaeche,3 H. Okamura,4 M. Kurimoto,5 and G. Dougan1

Department of Biochemistry, Imperial College of Science, Technology and Medicine, South Kensington, London SW7 2AZ,1 School of Microbiological, Immunological and Virological Sciences, Medical School, University of Newcastle, Newcastle Upon Tyne NE2 4HH,3 and Department of Clinical Veterinary Medicine, Madingley Road, Cambridge CB3 OES,2 United Kingdom, and Hyogo College of Medicine, Nishinomiya,4 and Fujisaki Institute, Hayashibara Biochemical Laboratories Inc., Okayama,5 Japan

Received 24 April 1998/Returned for modification 10 June 1998/Accepted 10 November 1998

Spleen and peritoneal macrophages obtained from innately resistant A/J mice released low levels of interleukin 18 (IL-18) upon infection with Salmonella typhimurium C5 RP4. Incubating the cells with recombinant gamma interferon (rIFN-gamma ) enhanced IL-18 production. A/J mice treated in vivo with anti-IL-18 antibodies showed impaired resistance to infection, with increased bacterial loads in the liver and spleen. Administration of rIL-18 could protect A/J mice from challenge with a lethal dose of virulent salmonellae, with a dramatic reduction in bacterial numbers in the tissues. rIL-18 administration did not ameliorate the disease in IFN-gamma -R-/- mice. IL-18 proved to be required for IFN-gamma production by mouse splenocytes from conventional, scid, and rag-1-/- mice; in vivo IL-18 neutralization caused a decrease in circulating IFN-gamma levels. Thus, IL-18 is a key factor in early host resistance to Salmonella and probably acts via IFN-gamma .

* Corresponding author. Mailing address: Department of Biochemistry, Imperial College of Science, Technology and Medicine, Exhibition Rd., South Kensington, London SW7 2AZ, United Kingdom. Phone: 44 171 594 5254. Fax: 44 171 594 5255. E-mail: p.mastroeni{at}ic.ac.uk.

Infection and Immunity, February 1999, p. 478-483, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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