Role of Serotonin in the Regulation of Interferon-γ Production by Human Natural Killer Cells

ABSTRACT Monocytes, recovered directly from peripheral blood by counter-current centrifugal elutriation (CCE), were shown to provide two regulatory signals for induction of interferon-γ (IFN-γ) in natural killer (NK) cells in response to interleukin-2 (IL-2): an upregulating signal and an inhibitory signal. The inhibitory signal was time-dependent, irreversible, and operating on a pretranslational level, as indicated by the inability of enriched NK cells to accumulate IFN-γ mRNA in the presence of elutriated monocytes. Monocyte-induced inhibition of IFN-γ production was abrogated by the biogenic amine serotonin, acting via the 5-hydroxy-tryptamine, or serotonin (5-HT1A), subset of serotonin receptors (5-HTR). Thereby, serotonin effectively promoted IFN-γ production in the presence of monocytes. We conclude that serotonergic 5-HT1A receptors transduce signals that are required for NK cells to produce IFN-γ in response to IL-2.