Department of Anaesthesia and Peri -operative Medicine, The Alfred Hospital and Monash University, Melbourne, Vic., Australia.
Molecular Neurotrauma and Haemostasis laboratory, Australian Centre for Blood Diseases and Monash University, Melbourne, Vic., Australia.
Anaesthesia. 2018 Aug;73(8):955-966. doi: 10.1111/anae.14306. Epub 2018 May 28.
Dexamethasone is often administered to surgical patients for anti-emetic prophylaxis. This study examined the early (up to 24 h) in-vivo effects of dexamethasone (8 mg) to demonstrate the magnitude and temporal nature of changes on circulating peripheral blood mononuclear cell gene expression and activation in 10 healthy male volunteers. Blood samples were drawn at baseline, 2 h, 4 h and 24 h. Gene expression was measured using quantitative real-time polymerase chain reaction. Cytokine expression was measured using multiplex immuno-assays. Innate immune cell phenotypes were examined with flow cytometry. Dexamethasone resulted in rapid transient changes in immunophilin (p = 0.0247), plasminogen activator inhibitor-1 (p = 0.0004), forkhead box P3 (p = 0.0068) and dual specific phosphatase-1 (p = 0.0157) gene expression at 4 h compared with pre-dexamethasone. Plasma interleukin-10 levels increased within 2 h (p = 0.0071) and returned to baseline at 24 h. Reductions in classical (p = 0.0009) and intermediate monocytes (p = 0.0178) and dendritic cells (p = 0.0012) were followed by increases in the level of these populations at 24 h compared with pre-dexamethasone (classical monocytes p = 0.0073, intermediate monocytes p = 0.0271, dendritic cells p = 0.0142). There was a profound reduction in the mean fluorescence intensity of the maturation marker, human histocompatibility leucocyte antigen, at 24 h in all monocyte subsets (p = 0.0002 for classical and non-classical monocytes, p = 0.0001 for intermediate monocytes) and dendritic cells (p = 0.0001). This study confirms rapid transient effects of 8 mg dexamethasone on innate immune cells with the potential to alter the inflammatory response to surgery and provides support for the hypothesis that intra-operative administration may be both immunosuppressive and immune-activating in the immediate peri-operative period.
地塞米松常用于外科手术患者的止吐预防。本研究检查了地塞米松（8 毫克）的早期（最多 24 小时）体内作用，以证明 10 名健康男性志愿者循环外周血单个核细胞基因表达和激活的幅度和时间性质的变化。在基线、2 小时、4 小时和 24 小时采集血液样本。使用定量实时聚合酶链反应测量基因表达。使用多重免疫测定法测量细胞因子表达。使用流式细胞术检查固有免疫细胞表型。与地塞米松前相比，地塞米松在 4 小时导致免疫亲和素（p = 0.0247）、纤溶酶原激活物抑制剂-1（p = 0.0004）、叉头框 P3（p = 0.0068）和双特异性磷酸酶-1（p = 0.0157）基因表达的快速短暂变化。血浆白细胞介素 10 水平在 2 小时内升高（p = 0.0071），并在 24 小时内恢复基线。与地塞米松前相比，经典（p = 0.0009）和中间单核细胞（p = 0.0178）和树突状细胞（p = 0.0012）水平降低，随后在 24 小时内这些群体水平升高（经典单核细胞 p = 0.0073，中间单核细胞 p = 0.0271，树突状细胞 p = 0.0142）。在所有单核细胞亚群中，成熟标志物人组织相容性白细胞抗原的平均荧光强度在 24 小时时显著降低（经典和非经典单核细胞 p = 0.0002，中间单核细胞 p = 0.0001）和树突状细胞（p = 0.0001）。本研究证实 8 毫克地塞米松对固有免疫细胞的快速短暂作用，有可能改变手术的炎症反应，并为术中给药在围手术期即刻可能具有免疫抑制和免疫激活作用的假说提供支持。
