Modulation by Interferon-γ of the Production and Gene Expression of IL-1 Receptor Antagonist in Human Neutrophils

In this report, we show that interferon-γ (IFN-γ) modulates the production of IL-1ra in activated human neutrophils. In lipopolysaccharide-stimulated cells, IFN-γ increased the release of IL-1ra without modulating IL-1ra mRNA accumulation; under these conditions, IFN-γ only marginally enhanced IL-1rade novosynthesis, while IL-1ra was more efficiently secreted. In response to the formylated peptide, fMLP, neutrophils released small but significant amounts of IL-1ra, yet without an increase in IL-1ra mRNA over constitutive levels. Following IFN-γ treatment, however, the fMLP-elicited IL-1ra production was greatly potentiated, and this was accompanied by a transient increased accumulation of IL-1ra mRNA. Finally, opsonized yeast particles were found to induce IL-1ra formation at late incubation times, and prior treatment of neutrophils with IFN-γ moderately enhanced this response. Collectively, our results demonstrate that in neutrophils activated by different classes of agonists, IFN-γ modulates the release of IL-1ra by acting through distinct mechanisms.