Interferon (IFN)-α/β interleukin (IL)-12 and IL-18 coordinately induce production of IFN-γ during infection with herpes simplex virus type 2

Interferons (IFNs) are important mediators of antiviral activity. In this study we have investigated how production of IFN-gamma 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-alpha/beta) and interleukin (IL)-12, which was followed by production of IFN-gamma. IL-12 alone induced the most expression of IFN-gamma, which was augmented by cotreatment with IFN-alpha or IL-18, or combinations of IFN-alpha and IL-18. Moreover, neutralization of any of these cytokines in vitro strongly reduced the production of IFN-gamma, and neutralization of all three cytokines totally prevented HSV-2-induced IFN-gamma expression. Our data suggest that IFN-gamma production is induced during HSV-2 infection through the coordinated action of IFN-alpha/beta, IL-12 and IL-18.