Monocyte-mediated suppression of IL-2-induced NK-cell activation. Regulation by 5-HT1A-type serotonin receptors.

In the present study, the effects of serotonin on human natural killer (NK)-cell responsiveness to interleukin 2 (IL-2) was investigated. Concomitant treatment of human lymphocytes, enriched for NK effector cells by Percoll density-gradient centrifugation, with serotonin and IL-2 yielded a synergistic activation of NK-cell cytotoxicity (NKCC) in the presence but not in the absence of monocytes. The monocyte-dependent, regulatory effects of serotonin and/or IL-2 were prostaglandin-independent and could be reconstituted when monocytes, recovered by countercurrent centrifugal elutriation (CCE), were added to purified NK effector cells. The effects of serotonin on baseline and IL-2-activated NK cells were mimicked by the 5-HT1A receptor-specific agonists 8-OH-DPAT and (+)-ALK. Our data suggest that serotonin regulates NK-cell responsiveness to IL-2 via 5-HT1A receptors.