Effect of IL-4 and IL-13 on IFN- γ-induced production of nitric oxide in mouse macrophages infected with herpes simplex virus type 2

Interleukin (IL)-4 and IL-13 share a wide range of activities. Prominent among these is the ability to antagonize many interferon (IFN)- γ-induced activities. Here we demonstrate that IL-4 and IL-13 totally abrogate IFN- γ-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA and protein synthesis in a murine macrophage cell line. IFN- γ-treated cells infected with herpes simplex virus type 2 (HSV-2) or costimulated with tumor necrosis factor (TNF)- α showed an enhanced reactivity, which was only partially reduced by IL-4/13. The results indicate that IL-4 and IL-13 function by intervening with a step prior to iNOS transcription by antagonizing IFN- γ-induced signal(s) without counteracting synergistic virus- or TNF- α-induced signals. The beneficial effect of a sustained NO production in foci of virus infection is suggested.