Morphine inhibits complement receptor expression, phagocytosis and oxidative burst by a nitric oxide dependent mechanism

Abstract

Monocytes play a crucial role in the immune response by recognition, ingestion, and intracellular killing of microorganisms. We investigated whether morphine and fentanyl influence CD 11b and CD35 surface receptor expression, phagocytic activity and superoxide anion generation of monocytes in a whole blood flow cytometric assay. Whole blood of 13 healthy volunteers was incubated with different morphine and fentanyl concentrations. Expression of surface receptors CD 11b and CD35 was determined by fluorochrome-labelled antibodies. Phagocytic activity was assessed by ingestion of fluorescent bacteria. Conversion of dihydrorhodamin served for oxidative burst measurements. Morphine inhibited monocyte function in a concentration and time dependent manner. Morphine-induced changes were abolished by preincubation with the NO synthase inhibitor N-nitro-l-arginine as well as naloxone. Fentanyl failed to inhibit receptor expression, phagocytosis and reactive oxygen production by monocytes in clinically relevant as well as supraclinical concentrations. Our results suggest that these monocyte functions are inhibited by a morphine-stimulated NO release mediated by a mu opiate receptor subtype expressed on the surface of monocytes. In contrast, fentanyl did not share morphine's inhibitory effects on monocyte activity.