Eisenstein T K, Hilburger M E
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
J Neuroimmunol. 1998 Mar 15;83(1-2):36-44. doi: 10.1016/s0165-5728(97)00219-1.
The literature describing effects of morphine on cells of the immune system points to the clear conclusion that morphine given in vivo suppresses a variety of immune responses that involve the major cell types in the immune system, including natural killer (NK) cells, T cells, B cells, 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 expression, 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, preventing a conclusion as to the cell type being affected. Consistent effects on phagocytic cell function have been reported in rodents given morphine. In contrast, studies on immunomodulatory effects of morphine added 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 literature demonstrating downregulation of phagocytic cell function by morphine, particularly for human peripheral blood mononuclear cells (PBMCs) and PMNs. Phagocytosis, chemotactic responses, interleukin production, and generation of activated oxygen intermediates and arachidonic acid products have all been reported to be inhibited. On the contrary, the literature does not support direct effects of morphine on NK cell function, is inconclusive concerning effects on B cells, and provides limited 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 system observed after in vivo morphine are probably not direct, but mediated. In aggregate, the literature supports the existence of an in vivo neural-immune circuit through which morphine acts to depress the function of all cells of the immune system. Further, there is strong evidence that morphine can directly depress the function of macrophages and 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 immunopotentiation of immune function in in vitro assays using endogenous opioids. The possibility of different receptors for endogenous and exogenous opioids or of interactions among the activated opioid receptors may account for these opposing effects.
体内给予吗啡会抑制多种免疫反应，这些反应涉及免疫系统中的主要细胞类型，包括自然杀伤（NK）细胞、T细胞、B细胞、巨噬细胞和多形核白细胞（PMN）。在人类、猴子和啮齿动物中均报道了NK细胞活性的降低。同样，吗啡会抑制T细胞反应，这可通过抑制迟发型超敏反应和细胞毒性T细胞活性的诱导、调节T细胞抗原表达以及抑制对T细胞有丝分裂原的反应来评估。在人类、猴子和啮齿动物中均报道了对T细胞的影响。吗啡对B细胞活性的影响主要在啮齿动物中通过抗体形成试验进行测试，而该试验也需要巨噬细胞和T细胞，因此无法得出受影响细胞类型的结论。在给予吗啡的啮齿动物中报道了对吞噬细胞功能的一致影响。相比之下，关于体外将吗啡添加到免疫系统细胞上的免疫调节作用的研究表明，吗啡对其中一些细胞类型有显著影响，而对另一些则没有。有大量文献证明吗啡会下调吞噬细胞功能，特别是对人类外周血单核细胞（PBMC）和PMN。吞噬作用、趋化反应、白细胞介素产生以及活性氧中间体和花生四烯酸产物的生成均被报道受到抑制。相反，文献不支持吗啡对NK细胞功能有直接作用，关于对B细胞的作用尚无定论，且对T细胞作用的证据有限。体内和体外数据之间的差异表明，体内给予吗啡后观察到的对免疫系统某些细胞的影响可能不是直接的，而是介导的。总体而言，文献支持存在一种体内神经免疫回路，通过该回路吗啡可抑制免疫系统所有细胞的功能。此外，有强有力的证据表明吗啡可直接抑制巨噬细胞和PMN的功能，并调节一种T细胞表面标志物的表达。然而，几乎没有证据表明吗啡对NK细胞和B细胞有直接作用。使用内源性阿片类物质的体外试验中关于免疫功能增强的报道又带来了另一个复杂情况。内源性和外源性阿片类物质可能存在不同受体，或者激活的阿片类受体之间可能存在相互作用，这或许可以解释这些相反的作用。
