Histamine and histamine-receptor antagonists modify gene expression and biosynthesis of interferon γ in peripheral human blood mononuclear cells and in CD19-depleted cell subsets

The effect of histamine and histamine antagonists was examined on gene expression and biosynthesis of bacterial endotoxin (LPS) induced interferon gamma (IFN gamma) both in human peripheral mononuclear cells (PMBC) and in T-cell enriched fractions, We found, that histamine inhibited the LPS induced transcription of IFN I gene and biosynthesis of IFN gamma protein in PMBC and also in CD19-depleted cell populations. The inhibitory effect of histamine could be reversed by the H2 histamine receptor (HR2) antagonists cimetidine and ranitidine both in PMBC and in CD19-depleted cells, but not with triprolidine, an H1 receptor antagonist, suggesting that the inhibition of IFN gamma production is mediated through H2 receptors in these cell populations. In contrast to the inhibitory effect of histamine, cimetidine alone (in the absence of exogenous histamine) strongly stimulated both the IFN gamma mRNA and protein production, whereas this effect was hardly seen by and other H2 receptor blocker, ranitidine. This superinduction of IFN gamma gene by cimetidine disappeared if the CD19 + cells are removed from PMBC. These results suggest, that inhibition of IFN I gene expression by histamine is a direct effect of histamine on H2 receptor of T lymphocytes; however, the superinduction of IFN gamma by cimetidine requires the presence of other (probably primarily B) cell subsets. (C) 1999 Elsevier Science B.V. All rights reserved.