INTERFERON-ALPHA BETA INHIBITS THE APOPTOSIS INDUCED BY LIPOPOLYSACCHARIDE AND INTERFERON-GAMMA IN MURINE PERITONEAL-MACROPHAGES/

Challenge of elicited peritoneal macrophages with lipopolysaccharide ( LPS) and interferon-gamma (IFN-gamma) was followed by an apoptotic res ponse. These cells expressed cytokine-inducible nitric oxide synthase (iNOS) in response to these stimuli, and the NO released contributed m arkedly to the apoptotic death, as deduced from the increased viabilit y observed when iNOS activity was inhibited, The antiviral type I IFN (IFN-alpha/beta) downregulated the high levels of NO produced when cel ls were stimulated with suboptimal doses of LPS and IFN-gamma, Moreove r, IFN-alpha/beta also decreased cell death in LPS/IFN-gamma-activated cells, as determined by the reduction in the content of oligonucleoso mal DNA fragments, in the binding of annexin V to the plasma membrane, and in the amount of hypodiploid cells when analyzed by flow cytometr y after in vivo staining with propidium iodide, Kinetic analysis of th e protection exerted by IFN-alpha/beta against the apoptosis induced b y treatment with LPS and IFN-gamma showed that type I IFNs were very e ffective when added up to 1 h after IFN-gamma/LPS stimulation. Additio n of IFN-alpha/beta 4 h after stimulation with IFN-gamma/LPS failed co mpletely to prevent apoptosis. This inhibition of apoptosis elicited b y IFN-alpha/beta suggests the existence of a mechanism intended to imp rove macrophage viability in the course of certain viral infections.