Immunomodulation by indoleamines: serotonin and melatonin action on DNA and interferon-gamma synthesis by human peripheral blood mononuclear cells.

Different concentrations of indoleamines, serotonin and melatonin, inhibited phytohemagglutinin stimulated DNA synthesis. Thus, 10(-3) to 10(-4) M of either indoleamine acted at the optimal phytohemagglutinin concentration, while 10(-3) to 10(-7) M acted at suboptimal phytohemagglutinin levels. The serotonin effect was reversed by the serotonergic S1-S2 receptor antagonist methysergide but not by the S2 antagonist ketanserin. This indicates that only the S1 receptor is involved in the inhibitory effect. Inhibition of lymphoproliferation by indoleamines was also exerted on pokeweed mitogen and protein A from Staphylococcus aureus stimulations. Serotonin and melatonin also inhibited phytohemagglutinin and protein A from Staphylococcus aureus induction of interferon-gamma synthesis. The initial uptake of Ca2+ was not affected by indoleamines, suggesting that it is not the mechanism of their inhibitory effects. As interferon-gamma induced tryptophan uptake by T lymphocyte- and macrophage-depleted populations, and tryptophan is the metabolic precursor of serotonin and melatonin, a new immunoregulatory circuit is postulated.