Peterson P K, Sharp B, Gekker G, Brummitt C, Keane W F
J Immunol. 1987 Jun 1;138(11):3907-12.
Opiate addiction and stress have been associated with altered immune responses. In this study, we evaluated the influence of morphine and the stress responsive opioid peptide beta-endorphin (beta-END) on O-2 and H2O2 production by cultured human peripheral blood mononuclear cells. Exposure of these cells during 48 hr of culture to morphine and beta-END at pharmacologically (10(-8) M) and physiologically (10(-12) M) relevant concentrations, respectively, markedly suppressed peripheral blood mononuclear cell O-2 and H2O2 release in response to the respiratory burst stimuli opsonized zymosan and phorbol myristate acetate. Both opioids also induced a minimal, but statistically significant, increase in resting O-2 and H2O2 generation. The modulatory effects of morphine and beta-END on peripheral blood mononuclear cell oxygen metabolism appeared to involve a classical opioid receptor, because opioid activity was blocked by naloxone and was not observed with N-acetylated-beta-END. Using purified lymphocyte and monocyte preparations, we determined that although opioids directly increase monocyte-resting oxygen metabolism, lymphocytes are the primary target cell in opioid-mediated suppression of monocyte respiratory burst activity. The release of a suppressive product from opioid-triggered lymphocytes was inhibited by cyclosporine. Based on the results of this study, we propose that opioid-mediated suppression of mononuclear phagocyte respiratory burst activity is another factor to be considered in the immunodeficiency of opiate addiction and stress.
阿片类药物成瘾和应激与免疫反应改变有关。在本研究中，我们评估了吗啡和应激反应性阿片肽β-内啡肽（β-END）对培养的人外周血单个核细胞产生超氧阴离子（O₂）和过氧化氢（H₂O₂）的影响。在培养48小时期间，分别将这些细胞暴露于药理学相关浓度（10⁻⁸ M）和生理学相关浓度（10⁻¹² M）的吗啡和β-END，显著抑制了外周血单个核细胞对呼吸爆发刺激物调理酵母聚糖和佛波酯肉豆蔻酸酯的O₂和H₂O₂释放。两种阿片类药物还诱导静息状态下O₂和H₂O₂生成量有微小但具有统计学意义的增加。吗啡和β-END对外周血单个核细胞氧代谢的调节作用似乎涉及经典阿片受体，因为阿片活性被纳洛酮阻断，而N-乙酰化-β-END未观察到这种作用。使用纯化的淋巴细胞和单核细胞制剂，我们确定尽管阿片类药物直接增加单核细胞静息氧代谢，但淋巴细胞是阿片介导的抑制单核细胞呼吸爆发活性的主要靶细胞。环孢素抑制了阿片触发的淋巴细胞释放抑制性产物。基于本研究结果，我们提出阿片介导的抑制单核吞噬细胞呼吸爆发活性是阿片类药物成瘾和应激免疫缺陷中另一个需要考虑的因素。
