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

Background: Opioids are used by patients who have conditions ranging from the acute pain of surgery and chronic cancer pain to substance abuse. Despite their widespread use and considerable experimental data about 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 including a 24-h intravenous infusion in the hospital. Peripheral blood was drawn for immune function studies at five measurement times before, during, and after morphine exposure. Peripheral blood mononuclear cells were tested for acute and gamma-interferon-stimulated natural killer cell 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 after the onset of intravenous morphine exposure. Suppression of NKCC persisted for 24 h after termination of morphine infusion in a ''high''-dose study group. gamma-Interferon-stimulated NKCC and antibody-dependent cell cytotoxicity were also decreased after 24 h of intravenous morphine exposure. No effect on Pc receptor expression was observed. Mean virus antigen production after lymphocyte infection with human immunodeficiency virus was not increased (24 100 ng/ml after morphine vs. 43 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.