title: Opioid-mediated suppression of cultured peripheral blood mononuclear cell respiratory burst activity.
abstract: 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.
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology; D004723:Endorphins / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011957:Receptors, Opioid / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan; D001615:beta-Endorphin
chemical_list: D003524:Cyclosporins; D004723:Endorphins; D011957:Receptors, Opioid; D013481:Superoxides; D009270:Naloxone; D001615:beta-Endorphin; D009020:Morphine; D015054:Zymosan; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate