IL-18 (IFN-gamma-inducing factor) regulates early cytokine production in, and promotes resolution of, bacterial infection in mice.

Abstract

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.

• Authors: E Bohn, A Sing, R Zumbihl, C Bielfeldt, H Okamura, M Kurimoto, J Heesemann, I B Autenrieth
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 160 Issue 1 Pg. 299-307 (Jan 01 1998) ISSN: 0022-1767 [Print] United States
• PMID: 9551984 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-18
• Interleukin-12
• Interferon-gamma

Topics

• 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 Infections (immunology)
• Yersinia enterocolitica