Department of Pharmacology, University of Milano, Italy.
Curr Pharm Des. 2012;18(37):6034-42. doi: 10.2174/138161212803582496.
This review provides an overview of the immunological effects of commonly used analgesic opioid drugs, focusing mainly on two aspects: the mechanisms involved and the potential clinical relevance. The immunomodulatory effects of morphine have been characterized in animal and human studies. Morphine decreases the effectiveness of both natural and acquired immunity, interfering with intracellular pathways involved in immune regulation, both directly and indirectly via the activation of central receptors. The mechanisms and the targets at the basis of opioid-induced immunomodulation have started to be elucidated, demonstrating an interaction between opioid receptors and several molecules involved in the complex and well orchestrated immune response, such as transcription factors and receptors of both myeloid and lymphoid cells. Due to their widespread and expanding use, the immunological effects of opioid are receiving considerable attention because of concerns that opioid-induced changes in the immune system may affect the outcome of surgery or of variety of disease processes, including bacterial and viral infections and cancer. It is also emerging that not all opioids induce the same immunosuppressive effects and evaluating each opioid profile is important for appropriate analgesic selection. The impact of the opioid-mediated immune effects could be particularly dangerous in selective vulnerable populations, such as the elderly or immunocompromised patients. Indeed, it is evident that the possibility of reaching adequate and equivalent pain control by choosing either immunosuppressive drugs or drugs without an effect on immune responses may be an important consideration in opioid therapy.
这篇综述概述了常用镇痛阿片类药物的免疫学效应，主要关注两个方面：涉及的机制和潜在的临床相关性。吗啡的免疫调节作用已在动物和人体研究中得到证实。吗啡降低了天然和获得性免疫的效力，通过激活中枢受体，直接和间接干扰参与免疫调节的细胞内途径。阿片类药物诱导免疫调节的机制和靶点已开始阐明，表明阿片受体与参与复杂而协调的免疫反应的几种分子之间存在相互作用，如转录因子和髓样细胞和淋巴样细胞的受体。由于阿片类药物的广泛应用和不断扩大，其对免疫系统的免疫作用引起了相当大的关注，因为人们担心阿片类药物引起的免疫系统变化可能会影响手术或多种疾病过程的结果，包括细菌和病毒感染以及癌症。越来越明显的是，并非所有阿片类药物都引起相同的免疫抑制作用，评估每种阿片类药物的特征对于适当的镇痛选择很重要。阿片类药物介导的免疫效应的影响在选择性脆弱人群中可能特别危险，例如老年人或免疫功能低下的患者。事实上，通过选择具有免疫抑制作用的药物或对免疫反应没有影响的药物来达到足够和等效的疼痛控制的可能性可能是阿片类药物治疗中的一个重要考虑因素。
