ROLE OF INTERFERON-GAMMA IN THE PRIMING OF DECIDUAL MACROPHAGES FOR NITRIC-OXIDE PRODUCTION AND EARLY-PREGNANCY LOSS

We have previously shown that both priming and triggering signals were needed for nitric oxide production by decidual macrophages and that n itric oxide was responsible for embryo wastage. In this study, we inve stigated the role of IFN-gamma as the primary signal for macrophage ac tivation in early embryo loss. IFN-gamma-deficient (GKO) and heterozyg ous F1 control mice were injected with lipopolysaccharide (LPS) at day 7 of gestation. The results showed that the GKO mice were more resist ant to LPS-induced embryo loss than the wild type. This suggested that IFN-gamma was needed for LPS-induced embryo resorption and that decid ual macrophages from pregnant GKO mice were not primed and could not b e activated when given LPS. Further, the results showed that IFN-gamma mRNA was simultaneously expressed in the same embryos that also expre ssed mRNA markers for macrophage activation (TNF-alpha and iNOS), indi cating that macrophage activation could be a consequence of IFN-gamma production. Similarly, we investigated the role of IL-12 as a switch c ytokine capable of eliciting TH1-associated cytokine production includ ing IFN-gamma. The results showed that IL-12 mRNA expression was corre lated with IFN-gamma expression and macrophage activation. In this in vivo study, we showed for the first time that spontaneously increased decidual IFN-gamma expression is detrimental to embryo survival. (C) 1 997 Academic Press.