Interplay in Vitro Between ACTH, β-Endorphin, and Glucocorticoids in the Modulation of Spontaneous and Lymphokine-Inducible Human Natural Killer (NK) Cell Activity

Abstract Release of pro-opiomelanocortin (POMC)-derived peptides and glucocorticoids characterizes the activation of the hypothalamic–pituitary–adrenal (HPA) axis and represents a major adaptive response to stress. Both glucocorticoids and POMC-derived hormones are known to be crucial modifiers of the immune response. Natural killer (NK) cells are a lymphocyte subset deeply involved in immunosurveillance. Cortisol, the most important glucocorticoid hormone in humans, is a well-established inhibitor, whereas the two lymphokines, immune interferon (IFN-γ) and interleukin-2 (IL-2), are important physiological stimulators. In the present study, physiological as well as superphysiological concentrations of two POMC-derived peptides, ACTH and β-endorphin, were shown not only to affect in vitro spontaneous and lymphokine-inducible NK activity of peripheral blood mononuclear (PBM) cells, but also to modify cortisol-mediated inhibition. NK activity was measured in a 4-h cytotoxic assay using the cell line K562 as a target, after prior incubation with ACTH (10 −8 –l0 −12 M ) and β-endorphin (10 −8 –l0 −14 M ) in the presence or absence of cortisol(10 −6 M Al), IFN-γ (325 IU/ml), and IL-2 (25 IU/ml.). ACTH was ineffective in changing spontaneous NK activity at all concentrations, whereas β-endorphin enhanced NK cytotoxicity ( p p