Zhang Jun, Chen Liang, Sun Yunyun, Li Yuanhai
The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, Anhui, China.
The Second People's Hospital of Hefei Affiliated to Anhui Medical University, No. 246 Heping Road, Yaohai District, Hefei, 230011, Anhui, China.
Inflammopharmacology. 2017 Mar 17. doi: 10.1007/s10787-017-0338-z.
Tramadol is an analgesic drug and relieves pain through activating μ-opioid receptors and inhibiting serotonin and noradrenaline reuptake. Emerging evidence shows that it also stimulates immune cells, including NK cells, splenocytes, and lymphocytes, and elevates IL-2 production. However, it remains unknown whether and how tramadol directly affects macrophages. To answer these questions, we collected human umbilical cord blood, isolated macrophages, and examined their responses to tramadol. Although tramadol did not alter resting macrophages and the antigen-presenting function in lipopolysaccharide-activated macrophages, it regulated M1 and M2 macrophages, which are, respectively, transformed by IFN-γ and IL-4. Interestingly, tramadol inhibits production and secretion of cytokines in M1 macrophages, but facilitates the production of inflammation-responding molecules, synthesized in M2 macrophages. We also found that STAT6 cascade pathway in M2 macrophages was significantly enhanced by tramadol. Therefore, this study reveals that tramadol regulates inflammation by inhibiting M1 macrophages (killing process), but promoting the function of M2 macrophages (healing process).
曲马多是一种镇痛药，通过激活μ-阿片受体以及抑制5-羟色胺和去甲肾上腺素再摄取来缓解疼痛。新出现的证据表明，它还能刺激免疫细胞，包括自然杀伤细胞、脾细胞和淋巴细胞，并提高白细胞介素-2的产生。然而，曲马多是否以及如何直接影响巨噬细胞仍不清楚。为了回答这些问题，我们采集了人脐带血，分离出巨噬细胞，并检测了它们对曲马多的反应。尽管曲马多不会改变静息巨噬细胞以及脂多糖激活的巨噬细胞的抗原呈递功能，但它能调节分别由干扰素-γ和白细胞介素-4转化而来的M1和M2巨噬细胞。有趣的是，曲马多抑制M1巨噬细胞中细胞因子的产生和分泌，但促进M2巨噬细胞中合成的炎症反应分子的产生。我们还发现，曲马多能显著增强M2巨噬细胞中的信号转导及转录激活因子6（STAT6）级联途径。因此，本研究表明，曲马多通过抑制M1巨噬细胞（杀伤过程）来调节炎症，但促进M2巨噬细胞（愈合过程）的功能。
