Products of stimulated monocytes enhance the activity of interferon-gamma.
We have investigated the interaction of interferon-gamma (IFN-gamma) with monocytes or products of stimulated monocytes. We have shown that IFN-gamma does not stimulate IFN-alpha production in monocytes. Staphylococcus aureus (SAC) but not lipopolysaccharide (LPS) induced IFN-alpha secretion by monocytes. However, it was observed that supernatants of monocytes stimulated with IFN-gamma in combination with either LPS or SAC had higher levels of antiviral activity than supernatants of monocytes stimulated only with IFN-gamma. Moreover, the degree of enhancement of antiviral activity was dependent on the dose of either LPS or SAC used to stimulate the monocytes. Supernatants of monocytes stimulated with LPS or SAC enhanced the antiviral activity of IFN-gamma but not IFN-alpha. Thus, LPS- or SAC-stimulated monocytes produced a factor(s) that augmented the biological activity of IFN-gamma. To identify the factor within stimulated monocyte supernatants that was responsible for this enhancement, several monokines were added to IFN-gamma. Tumor necrosis factor (TNF) significantly increased the antiviral activity of IFN-gamma, although TNF by itself had no antiviral activity. Interleukin 1 (IL-1) or granulocyte-monocyte colony-stimulating factor (GM-CSF) did not enhance the activity of IFN-gamma. Our data indicate that the interaction between IFN-gamma and monocytes is bidirectional. Not only can IFN-gamma activate monocytes, but products of stimulated monocytes also enhance the biological activities of IFN-gamma.
Gerrard
T L
TL
Division of Cytokine Biology, FDA, Bethesda, MD 20892.
Dyer
D R
DR
Enterline
J C
JC
Zoon
K C
KC
D002460:Cell Line; D004357:Drug Synergism; D006801:Humans; D007202:Indicators and Reagents; D007369:Interferon Inducers / Q000494:pharmacology; D007370:Interferon Type I / Q000096:biosynthesis / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D013211:Staphylococcus aureus
D007202:Indicators and Reagents; D007369:Interferon Inducers; D007370:Interferon Type I; D008070:Lipopolysaccharides; D007371:Interferon-gamma