Ma K, Ma P, Lu H, Liu S, Cao Q
Department of Anesthesiology, The Fourth Hospital of Shijiazhuang, Shijiazhuang, China.
Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang, China.
Scand J Immunol. 2017 May;85(5):343-349. doi: 10.1111/sji.12538.
The aim of this study was to investigate the effects and the underlying mechanisms of fentanyl anaesthetic on T lymphocytes isolated from human umbilical cord blood in vitro. The percentages of CD4 , CD8 and regulatory T (Treg) cells in human umbilical cord blood mononuclear cells (UBMC) treated with fentanyl in vitro were analysed by flow cytometry. The levels of cytokines IFN-γ, IL-2, IL-4 and IL-17 secreted by activated CD4 T cells were measured by ELISA assays. Expressions of MAPK and NF-κB signalling pathway proteins were determined by Western blotting. Effects of fentanyl on IKK and p65 expression promoter activities were analysed by luciferase assay. Fentanyl decreased the percentages and amounts of CD4 , CD8 and Foxp3 Treg T lymphocyte subsets in UBMCs in a dose-dependent manner. Fentanyl inhibited the proliferation and induced apoptosis of activated CD4 T cells dose dependently. Fentanyl could not reverse the increase of cell proliferation in activated groups to be equivalent with those in inactivated group. Secretions of IFN-γ, IL-2 and IL-4 cytokines were significantly decreased by moderate to high dose of fentanyl compared with controls. No significant differences were observed in protein expressions of MAPK pathway. In addition, fentanyl suppressed the IKKs-mediated activation of NF-κB. This study demonstrates that fentanyl exerts immunosuppressive effects on T lymphocytes obtained from UBMCs. Thus, the clinical application of fentanyl would not only relieve pain caused by surgery but regulate immune responses post-operation possibly through inhibition of IKKs-mediated NF-κB activation.
本研究旨在探讨芬太尼麻醉剂对体外分离的人脐带血T淋巴细胞的影响及其潜在机制。采用流式细胞术分析体外经芬太尼处理的人脐带血单个核细胞（UBMC）中CD4、CD8和调节性T（Treg）细胞的百分比。通过ELISA检测法测定活化的CD4 T细胞分泌的细胞因子IFN-γ、IL-2、IL-4和IL-17的水平。采用蛋白质印迹法检测MAPK和NF-κB信号通路蛋白的表达。通过荧光素酶测定法分析芬太尼对IKK和p65表达启动子活性的影响。芬太尼以剂量依赖性方式降低了UBMC中CD4、CD8和Foxp3 Treg T淋巴细胞亚群的百分比和数量。芬太尼剂量依赖性地抑制活化的CD4 T细胞的增殖并诱导其凋亡。芬太尼无法将活化组的细胞增殖增加逆转至与未活化组相当的水平。与对照组相比，中高剂量的芬太尼显著降低了IFN-γ、IL-2和IL-4细胞因子的分泌。MAPK信号通路的蛋白表达未观察到显著差异。此外，芬太尼抑制IKK介导的NF-κB活化。本研究表明，芬太尼对从UBMC获得的T淋巴细胞具有免疫抑制作用。因此，芬太尼的临床应用不仅可以缓解手术引起的疼痛，还可能通过抑制IKK介导的NF-κB活化来调节术后免疫反应。
