Opioid therapy and immunosuppression: a review.
Opioid therapy and immunosuppression: a review.
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DOI：
10.1097/01.mjt.0000132250.95650.85
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发表时间：
2004-09-01
影响因子：
4.2
通讯作者：
Benyamin, Ramsun
中科院分区：
文献类型：
--
作者：
Vallejo, Ricardo;de Leon-Casasola, Oscar;Benyamin, Ramsun
阿片类药物调节免疫系统的想法并不新鲜。到了19世纪末，Cantacuzene使用吗啡来抑制细胞免疫并降低豚鼠对细菌感染的抵抗力。外源性阿片类药物介导免疫抑制，而内源性阿片类药物则发挥相反的作用。已知急性和慢性阿片类药物给药对体液和细胞免疫反应具有抑制作用，包括抗体产生、自然杀伤细胞活性、细胞因子表达和吞噬活性。阿片类药物的行为类似于细胞因子，通过与中枢神经系统和外周的受体相互作用来调节免疫反应。中枢阿片类药物调节外周免疫功能的潜在机制可能涉及下丘脑-垂体-肾上腺轴和自主神经系统。人们越来越认识到中枢神经系统外阿片受体的存在。这些受体不仅在周围神经中被发现，也在免疫炎症细胞中被发现。阿片类药物介导的免疫抑制可能解释海洛因成瘾者感染发生率增加的原因。阿片类药物还可能通过减少 α 和 β 趋化因子（HIV 表达的重要抑制性细胞因子）的分泌，同时增加化学感受器 CCR5 和 CCR3（病毒的辅助受体）的表达来促进免疫缺陷病毒感染。外周免疫抑制至少部分是由位于中枢神经系统的阿片受体介导的，并且鞘内给药的阿片类药物不会发挥相同的免疫抑制作用，这一事实可能对那些接受长期阿片类药物治疗恶性和非恶性疼痛的患者具有重要的临床意义。
The idea that opioids modulate the immune system is not new. By the late 19th century, Cantacuzene, used morphine to suppress cellular immunity and lower the resistance of guinea pigs to bacterial infection. While exogenous opioids mediate immunosuppression, endogenous opiates exert opposite actions. Acute and chronic opioid administration is known to have inhibitory effects on humoral and cellular immune responses including antibody production, natural killer cell activity, cytokine expression, and phagocytic activity. Opiates behave like cytokines, modulating the immune response by interaction with their receptors in the central nervous system and in the periphery. Potential mechanisms by which central opiates modulate peripheral immune functions may involve both the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. The presence of opioid receptors outside the central nervous system is increasingly recognized. Those receptors have been identified not only in peripheral nerves but also in immune inflammatory cells. The immunosuppression mediated by opiates may explain the increased incidence of infection in heroin addicts. Opiates may also promote immunodeficiency virus infection by decreasing the secretion of alpha and beta chemokines (important inhibitory cytokines for the expression of HIV) and at the same time increasing the expression of chemoreceptors CCR5 and CCR3, coreceptors for the virus. The fact that peripheral immunosupression is mediated at least in part by opioid receptors located in the central nervous system and that intrathecally administered opioids do not exert the same immunosuppressive effects may have important clinical implications for those patients receiving long-term opioid therapy for malignant and nonmalignant pain.