EFFECT OF IL-4 AND IL-13 ON IFN-GAMMA-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, Promine nt among these is the ability to antagonize many interferon (IFN)-gamm a-induced activities. Here we demonstrate that IL-4 and IL-13 totally abrogate IFN-gamma-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA and protein synthesis in a murine ma crophage cell line, IFN-gamma-treated cells infected with herpes simpl ex virus type 2 (HSV-2) or costimulated with tumor necrosis factor (TN F)-alpha showed an enhanced reactivity, which was only partially reduc ed by IL-4/13. The results indicate that IL-4 and IL-13 function by in tervening with a step prior to iNOS transcription by antagonizing IFN- gamma-induced signal(s) without counteracting synergistic virus- or TN F-alpha-induced signals, The beneficial effect of a sustained NO produ ction in foci of virus infection is suggested. (C) 1997 Federation of European Biochemical Societies.