IL-18 (IFN-{gamma}-Inducing Factor) Regulates Early Cytokine Production in, and Promotes Resolution of, Bacterial Infection in Mice

IL-12-induced IFN-gamma production is essential for clearance of Yersinia enterocolitica infection. Similar to IL-12, the recently described cytokine IL-18 (IFN-gamma-inducing factor) is produced by macrophages and induces IFN-gamma production in spleen cells. Therefore, we have investigated the rol...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1998-01, Vol.160 (1), p.299-307
Main Authors: Bohn, Erwin, Sing, Andreas, Zumbihl, Robert, Bielfeldt, Claudia, Okamura, Haruki, Kurimoto, Masashi, Heesemann, Jurgen, Autenrieth, Ingo B
Format: Article
Language:English
Subjects:
Animals
Cytokines - physiology
Female
Interferon-gamma - physiology
Interleukin-12 - physiology
Interleukin-18
Macrophage Activation
Macrophages, Peritoneal - immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Spleen - microbiology
Yersinia enterocolitica
Yersinia Infections - immunology
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Summary:IL-12-induced IFN-gamma production is essential for clearance of Yersinia enterocolitica infection. Similar to IL-12, the recently described cytokine IL-18 (IFN-gamma-inducing factor) is produced by macrophages and induces IFN-gamma production in spleen cells. Therefore, we have investigated the role of IL-18 in Yersinia infection of mice. Heat-killed yersinia-triggered IL-18-promoted IFN-gamma production of splenocytes was predominantly dependent on endogenous IL-12 production, whereas IL-12-promoted IFN-gamma production was not IL-18 dependent. IL-18-induced IFN-gamma production was to a higher degree dependent on IFN-gammaR-mediated mechanisms and in synergism with IL-2 resulted in at least fivefold higher IFN-gamma levels as compared with the combination of IL-12 plus IL-2. Analysis of the effect of IL-18 on IL-12 production of LPS-stimulated peritoneal macrophages revealed that IL-18 decreased LPS-induced IL-12 production, indicating that IL-18 might be involved in negative regulation of IL-12 production. In vivo studies revealed that Yersinia-resistant C57BL/6 mice expressed fourfold higher IL-18 mRNA levels than did susceptible BALB/c mice. Administration of anti-IL-18 Abs caused a 100- to 1000-fold increase in bacterial counts in the spleen of infected mice but did not change IFN-gamma production levels. Taken together, our data demonstrate that IL-18 is involved in regulation of cytokine production during the early phase of bacterial infections as well as in clearance of Yersinia infection.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.160.1.299