Opioid-mediated suppression of cultured peripheral blood mononuclear cell respiratory burst activity.

Opiate addiction and stress have been associated with altered immune responses. In this study, we evaluated the influence of morphine and the stress responsive opioid peptide beta-endorphin (beta-END) on O-2 and H2O2 production by cultured human peripheral blood mononuclear cells. Exposure of these cells during 48 hr of culture to morphine and beta-END at pharmacologically (10(-8) M) and physiologically (10(-12) M) relevant concentrations, respectively, markedly suppressed peripheral blood mononuclear cell O-2 and H2O2 release in response to the respiratory burst stimuli opsonized zymosan and phorbol myristate acetate. Both opioids also induced a minimal, but statistically significant, increase in resting O-2 and H2O2 generation. The modulatory effects of morphine and beta-END on peripheral blood mononuclear cell oxygen metabolism appeared to involve a classical opioid receptor, because opioid activity was blocked by naloxone and was not observed with N-acetylated-beta-END. Using purified lymphocyte and monocyte preparations, we determined that although opioids directly increase monocyte-resting oxygen metabolism, lymphocytes are the primary target cell in opioid-mediated suppression of monocyte respiratory burst activity. The release of a suppressive product from opioid-triggered lymphocytes was inhibited by cyclosporine. Based on the results of this study, we propose that opioid-mediated suppression of mononuclear phagocyte respiratory burst activity is another factor to be considered in the immunodeficiency of opiate addiction and stress.