Mo. Adelson et al., EFFECTS OF THE OPIOID ANTAGONIST NALOXONE ON HUMAN NATURAL-KILLER-CELL ACTIVITY IN-VITRO, Israel journal of medical sciences, 30(9), 1994, pp. 679-684
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.