| Abstract: | The secretion of interferon-γ (IFN-γ) by natural killer (NK) cells following in vitro stimulation with interleukin-2 (IL-2) is inhibited by co-incubation with autologous monocytes at 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-γ was operating at a pre-translational level, this was indicated by the inability of CD 56+-enriched natural killer cells to accumulate IFN-γ 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-γ production. We thereby conclude that histamine behaves synergistically with IL-2 at a transcriptional level to induce IFN-γ even in an admixture of NK cells and monocytes. |
