The Effect of Gamma Interferon on Interleukin 1 Release of Human Monocytes

Abstract

The effect of gamma interferon (IFN-gamma) on interleukin 1 (IL-1) production by human monocytes induced either by bacterial lipopolysaccharide (LPS) or silica dust was examined. Release of biologically active IL-1 from LPS-activated monocytes was enhanced in a dose-dependent manner with IFN-gamma. The augmenting effect of IFN-gamma was most marked in monocytes stimulated with a sub-optimal dose of LPS (1 ng/ml). IFN-gamma delivered the augmenting effect only if present at the beginning of the IL-1 induction. The IL-1 released in the presence of IFN-gamma was characterized by gel filtration on fast protein liquid chromatography (FPLC) and by isoelectric focusing; the augmented form of IL-1 was a 17 kDa molecule, with pI 7, i.e. IL-1 beta. In contrast to these data, IFN-gamma had a decreasing effect on IL-1 release by monocytes stimulated with silica dust; in monocyte cultures stimulated with a sub-optimal dose of silica (100 micrograms/ml), only minute amounts of biologically active IL-1 were released in the presence of IFN-gamma. With higher silica concentrations the decreasing effect was less strong. The effects of IFN-gamma on the levels of IL-1 beta mRNA were also analysed. IFN-gamma did not alter the accumulation of IL-1 beta mRNA in LPS-stimulated monocytes. In contrast, in silica-stimulated monocytes IFN-gamma reduced the steady-state levels of IL-1 beta mRNA. Thus, these data indicate that, depending on the stimulating agent, IFN-gamma either down- or up-regulates IL-1 production; the former takes place mainly at the level of transcription, while the latter occurs with post-transcriptional mechanisms.