The role of reactive oxygen metabolites in the transcriptional regulation of IFN-gamma gene expression by histamine in NK cells following IL-2 stimulation

The secretion of interferon-gamma (IFN-gamma) by natural killer (NK) cells following in vitro stimulation with interleukin-2 (IL-2) is inhibited by co-incubation with autologous monocytes al a transcriptional level by more than sixty-fold. In this study, we investigate the nature of the inhibitory signal and particularly the role of reactive oxygen metabolites (ROMs). It was found that the inhibition of IFN-gamma was operating at a pre-translational level, this was indicated by the inability of CD 56(+)-enriched natural killer cells to accumulate IFN-gamma mRNA in the presence of elutriated monocytes. Both catalase, a scavenger of hydrogen peroxide and histamine, a biogenic amine which inhibits the generation of ROMs by monocytes, strongly abrogated the inhibition of IFN-gamma production. We thereby conclude that histamine behaves synergistically with IL-2 at a transcriptional level to induce IFN-gamma even in an admixture of NK cells and monocytes. (C) 1996 Academic Press Limited