MORPHINE INHIBITS SPONTANEOUS AND CYTOKINE-ENHANCED NATURAL-KILLER-CELL CYTOTOXICITY IN VOLUNTEERS

Background: Opioids are used by patients who have conditions ranging f rom the acute pain of surgery and chronic cancer pain to substance abu se. Despite their widespread use and considerable experimental data ab out them, little is known about how opioids may alter in vivo immunity in humans. This study was designed to evaluate the in vivo effect of morphine on human peripheral blood immune functions. Methods: Healthy volunteers underwent continuous exposure to morphine for 36 h includin g a 24-h intravenous infusion in the hospital. Peripheral blood was dr awn for immune function studies at five measurement times before, duri ng, and after morphine exposure. Peripheral blood mononuclear cells we re tested for acute and gamma-interferon-stimulated natural killer cel l cytotoxicity (NKCC), antibody-dependent cell cytotoxicity, antibody Pc receptor expression, and human immunodeficiency virus infectivity. Results: Significant suppression of NKCC was observed at 2 and 24 h af ter the onset of intravenous morphine exposure. Suppression of NKCC pe rsisted for 24 h after termination of morphine infusion in a ''high''- dose study group. gamma-Interferon-stimulated NKCC and antibody-depend ent cell cytotoxicity were also decreased after 24 h of intravenous mo rphine exposure. No effect on Pc receptor expression was observed. Mea n virus antigen production after lymphocyte infection with human immun odeficiency virus was not increased (24 100 ng/ml after morphine vs. 4 3 ng/ml before morphine; P = 0.17). Conclusions: These results suggest that morphine administration, at doses within the range of analgesic use, can cause measurable suppression of some components of the human cellular immune system.