Interferon-gamma potentiation of lipopolysaccharide-induced eicosanoid release from human monocytes

Interferon-gamma (IFN-gamma) can act to potentiate lipopolysaccharide (LPS)-stimulated processes in mononuclear phagocytes, including interleukin-1 release and tumoricidal activity. The present investigation examined the capacity of IFN-gamma to modulate LPS-stimulated prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) release from counterflow isolated human monocytes. The release of PGE2 and TxB2 was compared for cells incubated with IFN-gamma prior to treatment with LPS and for cells treated simultaneously with IFN-gamma and LPS. Treatment of cells with IFN-gamma prior to stimulation with LPS (10 micrograms/ml, Salmonella typhimurium) resulted in elevated prostaglandin E (by immunoassay) and [3H]PGE2 release from monocytes when compared with LPS-treated cultures. In contrast, IFN-gamma pretreatment did not potentiate labeled or immunoreactive TxB2 release from LPS-treated monocytes. IFN-gamma pretreatment without LPS stimulation did not result in elevated eicosanoid release over controls. In addition, continuous treatment of monocytes with both IFN-gamma and LPS did not result in greater release of PGE2 and TxB2 than the summed individual effects of IFN-gamma and LPS. These results indicate that IFN-gamma selectively potentiates LPS-stimulated arachidonic acid conversion to PGE2 and not TxB2 in human monocytes. This effect was observed only for monocytes pretreated with IFN-gamma prior to stimulation with LPS.