In vitro investigations of the effect of morphine and its metabolites on the phagocytosis of peripheral mononuclear cells

Abstract

Reports about an increased incidence of infection with facultative intracellular microorganisms suggest a depression of the macrophage/monocyte system. This explosive increase in oxidative metabolism can be measured by chemiluminescence. The aim of the present study was to investigate the influence of morphine and its metabolites morphine-3 (M-3-G) and 6-glucuronide (M-6-G) on the respiratory burst of the peripheral mononuclear cells (PCM). To explain the mechanism of the effect of morphine the antagonist naloxone was used. Furthermore, the effect was compared with that of bupivacaine and propranolol, known as drugs that stabilize the cell membranes. PMC were isolated from the blood of healthy young men by Ficol hypaque centrifugation. Four samples of 2 x 10(5) cells were incubated for at 37 degrees C and 10% CO(2) with either morphine, naloxone, bupivacaine, propranolol, M-3-G or M-6-G. After stimulation with oponised zymosan A, the lucigenin-dependent chemiluminescence was measured (n=8) in a biolumat (Berthold). Wilcoxon matched pairs (significance level p<0.05). Morphine inhibited the phagocytic activity of PMC only in concentrations >10(-7) mol/l. The metabolites M-3-G and M-6-G were considered to be similar based on tests using n=3. Naloxone itself significantly influences the emission of light solely in the high concentration of 10(-4) mol/l. Naloxone (10(-4) mol/l)+morphine(10(-5) mol/l) caused a greater inhibition than either of the substances alone. In comparison, the decreased chemiluminescence of morphine (10(-6) mol/l) was antagonized by naloxone (10(-5) mol/l). Naloxone in the same concentration was ineffective. The membrane stabilization caused by bupivacaine and propranolol did not change the chemiluminescence activity. Morphine had a decreasing effect on the respiratory burst of PCM only in concentrations that the human body reaches where renal clearance is reduced. In this situation the metabolites of morphine accumulate more than morphine itself and seem to have a similar effect. The weakening of phagocytosis might possibly be a direct effect of morphine and its metabolites. These investigations suggest that this phenomenon may be receptor dependent: the effect could be antagonized by naloxone, but naloxone itself caused a depression in high concentrations. In comparison the nonspecific stabilization of the membranes showed no such effect.