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Interferons (IFNs) are important mediators of antiviral activity. In this study we have investigated how production of IFN-γ is induced during herpes simplex virus type 2 (HSV-2) infection in murine peritoneal cells (PCs). We found that HSV-2 infection of thioglycolate-activated PCs from BALB/c mice rapidly led to expression of type 1 IFNs (IFN-α/β) and interleukin (IL)-12, which was followed by production of IFN-γ. IL-12 alone induced the most expression of IFN-γ, which was augmented by cotreatment with IFN-α or IL-18, or combinations of IFN-α and IL-18. Moreover, neutralization of any of these cytokines in vitro strongly reduced the production of IFN-γ, and neutralization of all three cytokines totally prevented HSV-2-induced IFN-γ expression. Our data suggest that IFN-γ production is induced during HSV-2 infection through the coordinated action of IFN-α/β, IL-12 and IL-18.
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