术中右美托咪定对辅助性T细胞1、辅助性T细胞2、辅助性T细胞17和调节性T细胞细胞因子水平及其平衡的免疫调节作用：一项前瞻性、随机、双盲、剂量反应性临床研究。
Immunomodulatory effects of intraoperative dexmedetomidine on T helper 1, T helper 2, T helper 17 and regulatory T cells cytokine levels and their balance: a prospective, randomised, double-blind, dose-response clinical study.
作者信息
Lee Jae-Myeong, Han Hyo-Jo, Choi Won-Kyu, Yoo Subin, Baek Soojin, Lee Jaemin
机构信息
Department of Anesthesiology and Pain Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271 Choenbo-ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea.
Department of Anesthesiology and Pain Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
出版信息
BMC Anesthesiol. 2018 Nov 8;18(1):164. doi: 10.1186/s12871-018-0625-2.
BACKGROUND
The ratio of T helper 1 (Th1) to T helper 2 (Th2) as well as T helper 17 (Th17) to regulatory T cells (Treg) represents the state and direction of immune response. Recent studies demonstrated that dexmedetomidine reduced the secretion of inflammatory cytokines. We performed this study to investigate the effect of different doses of intraoperative dexmedetomidine on the expression of Th1, Th2, T17 and Treg cytokines and their ratios.
METHODS
Seventy-five patients undergoing laparoscopic cholecystectomy were randomly separated into one of three groups: the full dose group (n = 25), in which dexmedetomidine was infused with a 1.0 μg/kg loading followed by an infusion of 0.5 μg/kg/min after anaesthetic induction, or the half dose group (n = 26), in which the dose was half of that of full dose group, or the saline group (n = 24) which was control. T cell cytokines were quantified by sandwich enzyme-linked immunoassay for blood samples taken after anaesthetic induction (T0), at the end of surgery (T1), and 60 min after surgery (T2). IFN-gamma/IL-4 and IL-17/IL-10, which represent the ratio of Th1/Th2 and Th17/Treg cytokines, respectively, were calculated as indices of immune cell levels based upon serum cytokines levels in place of direct measurements. C-reactive protein (CRP) concentrations were measured on the next day following surgery.
RESULTS
The full dose group was associated with higher ratios of IFN-gamma/IL-4 than those of half dose group and control [10.1 vs. 1.9 at T1 (P = 0.041) compared with half dose group, and 10.1 vs. 0.2 at T1 (P = 0.031), 7.4 vs. 0.1 at T2 (P = 0.025) compared with control]. IL-17/IL-10 ratios were higher in the full dose group than those in control [4.2 vs. 0.6 at T1 (P = 0.013), 3.0 vs. 0.3 at T2 (P = 0.011)]. The CRP levels were lower in the dexmedetomidine-treated groups in a dose-dependent manner.
CONCLUSIONS
Dexmedetomidine exhibits immunomodulatory effects, shifting the Th1/Th2 and T17/Treg cytokine balance toward Th1 and T17, respectively, in a dose-dependent pattern in patients with surgical and anaesthetic stress.
TRIAL REGISTRATION
Clinical Research Information Service, Republic of Korea (CRIS); KCT0000503 ; Registration date: Aug 13, 2012.
背景
辅助性T细胞1（Th1）与辅助性T细胞2（Th2）的比例以及辅助性T细胞17（Th17）与调节性T细胞（Treg）的比例代表免疫反应的状态和方向。最近的研究表明，右美托咪定可减少炎性细胞因子的分泌。我们进行这项研究以探讨术中不同剂量的右美托咪定对Th1、Th2、Th17和Treg细胞因子表达及其比例的影响。
方法
75例行腹腔镜胆囊切除术的患者被随机分为三组之一：全剂量组（n = 25），麻醉诱导后先静脉注射负荷剂量1.0 μg/kg右美托咪定，随后以0.5 μg/（kg·min）持续输注；或半剂量组（n = 26），其剂量为全剂量组的一半；或生理盐水组（n = 24）作为对照。在麻醉诱导后（T0）、手术结束时（T1）和术后60分钟（T2）采集血样，采用夹心酶联免疫吸附测定法定量T细胞细胞因子。分别计算IFN-γ/IL-4和IL-17/IL-10，它们分别代表Th1/Th2和Th17/Treg细胞因子的比例，作为基于血清细胞因子水平而非直接测量的免疫细胞水平指标。术后第二天测量C反应蛋白（CRP）浓度。
结果
全剂量组的IFN-γ/IL-4比例高于半剂量组和对照组[T1时为10.1比1.9（与半剂量组相比，P = 0.041），与对照组相比，T1时为10.1比0.2（P = 0.031），T2时为7.4比0.1（P = 0.025）]。全剂量组的IL-17/IL-10比例高于对照组[T1时为4.2比0.6（P = 0.013），T2时为3.0比0.3（P = 0.011）]。右美托咪定治疗组的CRP水平呈剂量依赖性降低。
结论
在有手术和麻醉应激的患者中，右美托咪定具有免疫调节作用，以剂量依赖的方式分别使Th1/Th2和T17/Treg细胞因子平衡向Th1和T17方向转变。
试验注册
大韩民国临床研究信息服务中心（CRIS）；KCT0000503；注册日期：2012年8月13日。
Zotero 插件