Department of Pain Treatment and Palliative Care, Jagiellonian University Medical College, 10 Sniadeckich St, PL 31-531 Krakow, Poland.
Department of Immunology, Jagiellonian University Medical College, 18 Czysta St, PL 31-121 Krakow, Poland.
Int Immunopharmacol. 2018 Jan;54:344-353. doi: 10.1016/j.intimp.2017.11.039. Epub 2017 Dec 1.
Opioid receptors are commonly expressed on various immune cells, macrophages especially. Thus, these cells are prone to stimulation with opioids, which seems to be responsible for opioid-induced immunomodulatory effects. While morphine, fentanyl and methadone influence on mouse immune response was recently studied, little is known about the potential immunomodulatory impact of buprenorphine and oxycodone.
The current research aimed to investigate the influence of buprenorphine and oxycodone on immune responses in mice under homeostatic conditions.
Repeated administration of morphine led to intensification of CHS response in actively sensitized mice, while buprenorphine or oxycodone administration exerted the opposite effect. Further, hapten-conjugated macrophages from mice treated with morphine, when transferred into naive recipients, induced more potent CHS response. The enhanced generation of reactive oxygen intermediates and nitric oxide by macrophages from mice treated with buprenorphine, oxycodone or morphine was also shown, along with increased release of IL-6, TNFα and TGFβ. Treatment with opioids altered expression of antigen phagocytosis and presentation markers. Finally, the inhibitory effect of morphine treatment on induction of humoral immunity by macrophages was demonstrated, while oxycodone failed to influence humoral immune response and buprenorphine actually enhanced B-cell activation.
Current observations confirm that macrophages greatly contribute to immunomodulatory effects of opioids. Studies on immunomodulation by opioids have great importance related to the evaluation of its beneficial and adverse effects on patient condition. Our research showed that oxycodone exerts the weakest immunomodulatory properties, allowing us to assume this drug as safer than morphine during prolonged therapy.
阿片受体通常在各种免疫细胞上表达，尤其是巨噬细胞。因此，这些细胞容易受到阿片类药物的刺激，这似乎是阿片类药物引起免疫调节作用的原因。虽然最近研究了吗啡、芬太尼和美沙酮对小鼠免疫反应的影响，但对丁丙诺啡和羟考酮的潜在免疫调节作用知之甚少。
本研究旨在探讨丁丙诺啡和羟考酮在稳态条件下对小鼠免疫反应的影响。
吗啡的重复给药导致主动致敏小鼠的 CHS 反应增强，而丁丙诺啡或羟考酮给药则产生相反的效果。此外，从接受吗啡治疗的小鼠中分离出的半抗原结合的巨噬细胞转移到未致敏的受体中，诱导出更强的 CHS 反应。还显示了丁丙诺啡、羟考酮或吗啡处理的巨噬细胞产生更多的活性氧中间体和一氧化氮，以及释放更多的 IL-6、TNFα 和 TGFβ。阿片类药物处理还改变了抗原吞噬和呈递标志物的表达。最后，证明了吗啡处理抑制巨噬细胞诱导体液免疫的作用，而羟考酮未能影响体液免疫反应，丁丙诺啡实际上增强了 B 细胞的激活。
目前的观察结果证实，巨噬细胞对阿片类药物的免疫调节作用有很大贡献。对阿片类药物免疫调节的研究具有重要意义，因为它涉及到评估其对患者病情的有益和不利影响。我们的研究表明，羟考酮表现出的免疫调节特性最弱，这使我们可以假设在长期治疗期间，与吗啡相比，该药物更安全。
