Kozlowski Michael, Nazimek Katarzyna, Wąsik Magdalena, Filipczak-Bryniarska Iwona, Bryniarski Krzysztof
Department of Immunology, Jagiellonian University Medical College, Czysta 18, Krakow, Poland.
Folia Med Cracov. 2017;57(2):15-30.
Macrophages (Mf) are a versatile group of phagocytic cells responsible for fulfilling a variety of immune functions, most notably for mounting the initial anti-microbial response and for the clearance of cellular debris and apoptotic bodies. The key processes for fulfilling these functions include the production of reactive oxygen intermediates (ROIs) and nitric oxide (NO). Mf also express a variety of receptors, including opioid, serotonin, and norepinephrine receptors, and thus can react to various substances. Our study aimed to examine the effects of oxycodone and buprenorphine on the production ROIs and NO by Mf from intraperitoneally-treated mice, as compared to the previously studied morphine, fentanyl, and methadone, as well as the effects of the analgesic adjuvants gabapentin, amitriptyline, and venlafaxine. ROIs was estimated via luminol and lucigenin dependent chemiluminescence assay, and NO secretion was estimated via a colorimetric method utilizing a modified Griess reaction. We observed an overall decrease in both ROIs and NO production by Mf from adjuvant-treated mice, especially with amitriptyline. Opioids, however, resulted in enhanced ROIs production and mixed NO secretion, with oxycodone and buprenorphine have the least immunomodulatory effects. As ROIs and NO are potent mediators of Mf activity during the innate immune response, our current results express great translational potential. Our results suggest that OPs administration may boost Mf anti-microbial response. On the other hand, during sterile in ammation, enhanced generation of ROIs by Mf influenced by opioids may increase the risk of tissue damage, but co-administration of adjuvants could abolish this adverse effect.
巨噬细胞（Mf）是一组多功能的吞噬细胞，负责履行多种免疫功能，最显著的是发起初始抗微生物反应以及清除细胞碎片和凋亡小体。实现这些功能的关键过程包括活性氧中间体（ROIs）和一氧化氮（NO）的产生。Mf还表达多种受体，包括阿片类、血清素和去甲肾上腺素受体，因此可以对各种物质做出反应。我们的研究旨在研究与先前研究的吗啡、芬太尼和美沙酮相比，羟考酮和丁丙诺啡对经腹腔注射处理的小鼠的Mf产生ROIs和NO的影响，以及镇痛佐剂加巴喷丁、阿米替林和文拉法辛的影响。通过鲁米诺和光泽精依赖的化学发光测定法估计ROIs，通过利用改良的格里斯反应的比色法估计NO分泌。我们观察到经佐剂处理的小鼠的Mf产生的ROIs和NO总体上有所减少，尤其是阿米替林处理的小鼠。然而，阿片类药物导致ROIs产生增加和NO分泌混合，羟考酮和丁丙诺啡的免疫调节作用最小。由于ROIs和NO是先天免疫反应期间Mf活性的有效介质，我们目前的结果具有很大的转化潜力。我们的结果表明，阿片类药物的给药可能会增强Mf的抗微生物反应。另一方面，在无菌炎症期间，受阿片类药物影响的Mf产生的ROIs增加可能会增加组织损伤的风险，但佐剂的联合给药可以消除这种不利影响。
