Interleukin 18 contributes to host resistance and gamma interferon production in mice infected with virulent Salmonella typhimurium

Pietro Mastroeni, S. Clare, S. Khan, J. A. Harrison, C. E. Hormaeche, H. Okamura, M. Kurimoto, G. Dougan

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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-γ) 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-γ-R(-/-) mice. IL-18 proved to be required for IFN-γ production by mouse splenocytcs from conventional, scid, and rag-1(-/-) mice; in vivo IL-18 neutralization caused a decrease in circulating IFN-γ levels. Thus, IL-18 is a key factor in early host resistance to Salmonella and probably acts via IFN-γ.

Original languageEnglish
Pages (from-to)478-483
Number of pages6
JournalInfection and Immunity
Issue number2
Publication statusPublished - 8 Feb 1999
Externally publishedYes

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