Interferon-γ Potentiation of Lipopolysaccharide-Induced Eicosanoid Release from Human Monocytes

Authors:
  • FNFrank C. Nichols
    Frank C. Nichols
  • SGScott W. Garrison
    Scott W. Garrison
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Abstract
Interferon-γ (IFN-γ) 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-γ 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-γ prior to treatment with LPS and for cells treated simultaneously with IFN-γ and LPS. Treatment of cells with IFN-γ prior to stimulation with LPS (10 μg/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-γ pretreatment did not potentiate labeled or immunoreactive TxB2 release from LPS-treated monocytes. IFN-γ pretreatment without LPS stimulation did not result in elevated eicosanoid release over controls. In addition, continuous treatment of monocytes with both IFN-γ and LPS did not result in greater release of PGE2 and TxB2 than the summed individual effects of IFN-γ and LPS. These results indicate that IFN-γ 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-γ prior to stimulation with LPS.

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