IL-15 induces IFN-beta and iNOS gene expression, and antiviral activity of murine macrophage RAW 264.7 cells

The effects of interleukine-15 (IL-15) on macrophage activation and antiviral activity have been investigated in this study. We have provided evidence that IL-15 stimulates murine macrophage RAW 264.7 cells to release nitric oxide (NO) and inhibit vaccinia virus (VV) replication in bystander human 293 cells in a dose-dependent manner. The IL-15-induced antiviral activity was partially mediated by NO, as blocking NO production by NO synthase (iNOS) inhibitor NG-monomethyl-L-arginine acetate (L-NMA) partially restored the virus replication. Interferon-gamma (IFN-gamma) was not detectable by ELISA in the cell supernatant of IL-15-activated macrophages or in the co-cultures of macrophages and infected bystander cells. Neutralizing anti-IFN-gamma, anti-IFN-gamma receptor R2, anti-TNF-alpha, or anti-IL-12 antibodies had no effect on NO production or antiviral activity. In contrast, neutralizing anti-IFN-alpha/beta antibody completely restored the VV replication and reduced the NO level to one third of that in the control. Elevated mRNA levels of IFN-beta and iNOS genes were detected in IL-15-activated RAW 264.7 cells by RT-PCR. Our data suggest that IL-15 is capable of inducing IFN-beta, which could participate in NO-mediated antiviral effect.