EFFECTS OF THE OPIOID ANTAGONIST NALOXONE ON HUMAN NATURAL-KILLER-CELL ACTIVITY IN-VITRO

Studies from several groups have shown that exogenous opiates as well as endogenous opioids may have direct or indirect effects on natural k iller cell (NK) activity. Both enhanced and reduced NK activity have b een reported in different in vivo and in vitro studies. The present st udy was performed to determine the effects of the opioid antagonist, n aloxone, on human NK activity in vitro. Human peripheral blood mononuc lear cells (PBMC) from 10 healthy normal subjects, as well as from 7 o therwise healthy methadone-maintained former heroin addicts, were used . These PBMC were incubated with a wide-concentration range (1 x 10(-1 2) to 1 x 10(-3)M) of (-)naloxone, the active enantiomer, and in paral lel assays with (+)naloxone, the inactive enantiomer, prior to and dur ing the NK activity assay. A significant seduction of NK activity by e ach enantiomer of naloxone was found only at very high concentrations, 1 x 10(-3)M (P<0.01) and above. These concentrations are much higher than plasma levels of naloxone reached in humans during any therapeuti c or research use of this opioid antagonist. This effect is probably d ue to an action at some site other than on classical opioid receptors. No effect was found at concentrations of naloxone below 1 x 10(-3)M. Thus, the data showed no naloxone-induced effects at concentrations of (-)naloxone which are sufficient to displace endogenous opioids from all types of classical opioid receptors, suggesting that the endogenou s opioids that remained intact and bound to PBMC in vitro do not have any measurable modulatory effect on NK cell cytotoxicity activity.