OPIOID MODULATION OF IMMUNE-RESPONSES - EFFECTS ON PHAGOCYTE AND LYMPHOID-CELL POPULATIONS

The literature describing effect of morphine on cells of the immune sy stem points to the clear conclusion that morphine given in vivo suppre sses a variety of immune responses that involve the major cell types i n the immune system, including natural killer (NK) cells, T cells, B c ells, macrophages and polymorphonuclear leukocytes (PMNs). Depression of NK cell activity has been reported in humans, monkeys and rodents. Similarly, responses of T cells are depressed by morphine, as assessed by inhibition of induction of delayed-type hypersensitivity reactions and cytotoxic T-cell activity, modulation of T-cell antigen expressio n, and depression of responses to T-cell mitogens. Effects on T cells have been reported in humans, monkeys and rodents. Effects of morphine on B-cell activity have mainly been tested in rodents using assays of antibody formation, which also require macrophages and T cells, preve nting a conclusion as to the cell type being affected. Consistent effe cts on phagocytic cell function have been reported in rodents given mo rphine. In contrast, studies on immunomodulatory effects of morphine a dded to cells of the immune system in vitro have shown robust effects on some of these cell types, but not others. There is a rich literatur e demonstrating downregulation of phagocytic cell function by morphine , particularly for human peripheral blood mononuclear cells (PBMCs) an d PMNs. Phagocytosis, chemotactic responses, interleukin production, a nd generation of activated oxygen intermediates and arachidonic acid p roducts have all been reported to be inhibited. On the contrary, the l iterature does not support direct effects of morphine on NK cell funct ion, is inconclusive concerning effects on B cells, and provides limit ed evidence for effects on T cells. The divergence between the in vivo and in vitro data suggests that effects on some cells in the immune s ystem observed after in vivo morphine are probably not direct, but med iated. In aggregate, the literature supports the existence of an in vi vo neural-immune circuit through which morphine acts to depress the fu nction of all cells of the immune system. Further, there is strong evi dence that morphine can directly depress the function of macrophages a nd PMNs, and modulate expression of one type of T-cell surface marker. There is, however, little evidence for direct effects of morphine on NK cells and B cells. A further complication emerges from reports of i mmunopotentiation of immune function in in vitro assays using endogeno us opioids. The possibility of different receptors for endogenous and exogenous opioids or of interactions among the activated opioid recept ors may account for these opposing effects. (C) 1998 Elsevier Science B.V.