Dezocine promotes T lymphocyte activation and inhibits tumor metastasis after surgery in a mouse model
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PHASE I STUDIES
Dezocine promotes T lymphocyte activation and inhibits tumor metastasis after surgery in a mouse model Qiang Song 1 & Geng Liu 2 & Dongyi Liu 3 & Chang Feng 3 Received: 16 December 2019 / Accepted: 6 March 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary Dezocine is an opioid analgesic with both μ-receptor agonist and antagonist activities. Administration of opioids influences the immune system through immune cells. Dendritic cells (DC) play crucial functions in inducing T cell response and mediating immune functions. DC surface displays several different opioid receptors whose expression is induced during DC maturation. We aimed to explore the effects of dezocine on DCs and T cells, as well as on tumor treatment. Mice were intraperitoneally administrated with increasing doses of dezocine (0.75, 1.25 and 2.0 mg/kg). Mouse bone marrow-derived dendritic cells (BMDCs) were then isolated from the bone marrow. The BMDC surface markers were evaluated by flow cytometry. T cell proliferation was assessed by the carboxyfluorescein succinimidyl ester assay. The number of mature DCs were increased by dezocine treatment in both human umbilical cord blood and mouse peripheral blood, suggesting that dezocine enhanced BMDC maturation. Dezocine-treated BMDCs promoted CD8+ T cell proliferation and cytotoxicity, while dezocine treatment inhibited tumor metastasis in mice. We therefore conclude that the administration of dezocine promotes BMDC maturation and inhibits tumor metastasis through elevating CD8+ T cell proliferation and cytotoxicity. Keywords Dezocine . Dendritic cell . T cell . Tumor metastasis
Introduction Postoperative pain is a surgical injury-induced stress on the physiology, psychology, and behavior of patients [1]. As a natural resistance phenomenon to external invasion, postoperative pain occurs during and even persists after the surgery [2]. Postoperative pain can enhance the body’s stress response and lead to declined immune functions, which in turn may contribute to tumor metastasis, recurrence, increased incidence of postoperative infections and adverse reactions, severely affecting the prognosis of patients [3]. There are several different strategies developed to alleviate postoperative pain, among which postoperative analgesia has several benefits, * Chang Feng [email protected] 1
Department of Anesthesiology, People’s Hospital of Caoxian, Fumin Street, Caoxian, Heze 274400, Shandong, China
2
Department of Anesthesiology, People’s Hospital of Liaocheng, No. 67 Dongchang West Street, Liaocheng 252000, Shandong, China
3
Department of Anesthesiology, the Second Hospital of Shandong University, No. 247 Bei yuan Street, Jinan 250033, Shandong, China
including accelerating wound healing, inhibiting tissue edema, decreasing incidence of incision infection and increasing oxygen content of subcutaneous tissues [4]. In addition, various anesthesia and drugs have been reported to influence the immune functions of tumor patients [5–7]. Dezocine is an opioid analge
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