Naloxone modulates NK-cell activity of human peripheral blood lymphocytes like an opioid agonist.
Naloxone at concentrations 10(-6) M to 10(-10) M modulated endogenous NK-activity in 11 of 14 samples of human peripheral blood lymphocytes after 18-hour incubation. The dose response usually showed two peaks, which varied with the donor. Enhancement was obtained in 6, suppression in 4, and both effects (depending on naloxone concentration) in 1 example; 3 donors were nonresponders. However, the overall effect of naloxone on endogenous NK activity was not statistically significant in the population as a whole. IL-2-stimulated NK-activity, was also altered by naloxone. The direction of the alteration depended on the degree of IL-2-induced NK-stimulation, and was donor-dependent. For example, naloxone enhanced NK-activity that had been stimulated by low IL-2 concentration (3 U/ml), but decreased NK-activity which had been stimulated by high (50 U/ml) IL-2 concentration. Naloxone 10(-7) M significantly reversed medium stimulation of NK activity, induced by 25 U/ml, in a group as a whole. Naloxone (10(-7) M to 10(-12) M) also modulated NK-activity stimulated by exogenous IFN alpha, as well as by endogenous, Poly-I.C-induced IFN. Decrease, or enhancement, depended on the degree of baseline NK-stimulation and varied with the donor. Short (2-hours) incubation with naloxone also resulted in the modulation of basal and IFN-stimulated NK-activity. Again, the effect varied with the donor and with the degree of lymphocyte activation. Thus, naloxone, the opioid receptor antagonist, modulated the NK-cell activity like opioid peptides, i.e. resembled an opioid agonist, in an individual, donor dependent fashion.
Martin-Kleiner
I
I
Ruder Bosković Institute, Department of Experimental Biology and Medicine, Zagreb, Croatia.
Gabrilovac
J
J
D000293:Adolescent; D000328:Adult; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004723:Endorphins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007372:Interferons / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D011070:Poly I-C / Q000494:pharmacology
D004723:Endorphins; D007376:Interleukin-2; D009270:Naloxone; D007372:Interferons; D011070:Poly I-C