Abstract
BackgroundThe 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.MethodsSeventy-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.ResultsThe 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.ConclusionsDexmedetomidine 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 registrationClinical Research Information Service, Republic of Korea (CRIS); KCT0000503; Registration date: Aug 13, 2012.
Highlights
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
There were no significant differences in the baseline (T0) cytokines concentrations among groups
The level of IL-4, a Th2 cytokine, declined during and after the surgery in the dexmedetomidine-treated groups compared with the baseline values: the reduction in IL-4 was in dose-dependent manner
Summary
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. 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. Studies in animals and clinical trials have shown that dexmedetomidine reduces the secretion of proinflammatory cytokines, which in turn alleviates systemic inflammatory response and even reduces mortality [4, 5]. These results suggest that harmful inflammatory responses can be modulated by administering an alpha-2 agonist to patients who are stressed and have an enhanced inflammatory reaction due to surgery and anaesthesia. The effects of different doses of dexmedetomidine on immunomodulation during perioperative period have not been examined
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