Role of Interferon-γ 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 nitric oxide was responsible for embryo wastage. In this study, we investigated the role of IFN-γ as the primary signal for macrophage activation in early embryo loss. IFN-γ-deficient (GKO) and heterozygous F1 control mice were injected with lipopolysaccharide (LPS) at day 7 of gestation. The results showed that the GKO mice were more resistant to LPS-induced embryo loss than the wild type. This suggested that IFN-γ was needed for LPS-induced embryo resorption and that decidual macrophages from pregnant GKO mice were not primed and could not be activated when given LPS. Further, the results showed that IFN-γ mRNA was simultaneously expressed in the same embryos that also expressed mRNA markers for macrophage activation (TNF-α and iNOS), indicating that macrophage activation could be a consequence of IFN-γ production. Similarly, we investigated the role of IL-12 as a switch cytokine capable of eliciting TH1-associated cytokine production including IFN-γ. The results showed that IL-12 mRNA expression was correlated with IFN-γ expression and macrophage activation. In thisin vivostudy, we showed for the first time that spontaneously increased decidual IFN-γ expression is detrimental to embryo survival.