Immunomodulation by indoleamines: Serotonin and melatonin action on DNA and interferon-? synthesis by human peripheral blood mononuclear cells

Abstract

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 fromStaphylococcus aureus stimulations. Serotonin and melatonin also inhibited phytohemagglutinin and protein A from Staphylococcus aureus induction of interferon-γ synthesis. The initial uptake of Ca²⁺ was not affected by indoleamines, suggesting that it is not the mechanism of their inhibitory effects. As interferon-γ 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.