Histamine suppresses neopterin production in the human myelomonocytoma cell line THP-1.
Histamine, an important inflammatory mediator in allergic diseases and asthma, was reported to have modulatory effects on T cells by down-regulating Th1-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 neopterin 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 with histamine, IFN-gamma and different concentrations of the H(2)-receptor antagonist cimetidine showed a clear antagonizing effect on neopterin formation. 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 mechanisms induced by IFN-gamma in monocytes/macrophages. Cimetidine, and possibly other H(2)-receptor antagonists, may reverse down-regulatory actions of endogenously formed histamine on activated monocytic cells.
Gruber
A
A
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, and Ludwig Boltzmann Institute for AIDS Research, Fritz-Pregl-Str. 3, A-6020, Innsbruck, Austria.
Murr
C
C
Wirleitner
B
B
Werner-Felmayer
G
G
Fuchs
D
D
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute; D019798:Neopterin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000276:immunology* / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D006633:Histamine Antagonists; D019798:Neopterin; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine