title: Tramadol differentially regulates M1 and M2 macrophages from human umbilical cord blood.
abstract: 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).
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Second People's Hospital of Hefei Affiliated to Anhui Medical University, No. 246 Heping Road, Yaohai District, Hefei, 230011, Anhui, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: The Second People's Hospital of Hefei Affiliated to Anhui Medical University, No. 246 Heping Road, Yaohai District, Hefei, 230011, Anhui, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, Anhui, China. Liyuanhai163lyh@163.com.
authors.forename: Yuanhai
authors.initials: Y
authors.lastname: Li
keywords: Inflammation; M1; M2; Macrophages; Tramadol