Histamine suppresses neopterin production in the human myelomonocytoma cell line THP-1

Histamine, an important inflammatory mediator in allergic diseases and asth ma, was reported to have modulatory effects on T cells by down-regulating T h1-type cell cytokines like interleukin 2 (IL-2) and interferon-gamma (IFN- gamma). In this study we examined the effect of histamine and the histamine -receptor antagonists cimetidine and diphenhydramine on the production of n eopterin after stimulation with IFN-gamma in the myelomonocytoma cell line THP-1. Increasing concentrations of histamine markedly suppressed IFN-gamma induced neopterin formation. Simultaneous preincubation of THP-1 cells wit h histamine, IFN-gamma and different concentrations of the H-2-receptor ant agonist cimetidine showed a clear antagonizing effect on neopterin formatio n. In contrast, the H-1-receptor antagonist diphenhydramine was not able to abrogate the suppressive effect of histamine on neopterin production. Our results suggest, that histamine may be a potent inhibitor of effects or mec hanisms induced by IFN-gamma in monocytes/macrophages. Cimetidine, and poss ibly other H-2-receptor antagonists, may reverse down-regulatory actions of endogenously formed histamine on activated monocytic cells. (C) 2000 Elsev ier Science B.V. All rights reserved.