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

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.

Role of α2-Adrenoceptors in Hypertension: Focus on Renal Sympathetic Neurotransmitter Release, Inflammation, and Sodium Homeostasis

“…Activation of α2-adrenoceptors expressed on dendritic cells reduces induction of T-cell proliferation (Araujo et al, 2019). In patients undergoing surgery, activation of α2-adrenoceptors shifted the Th1/Th2 and the Treg/Th17 cytokine balance toward a Th1 and Th17 response, respectively, suggesting a pro-inflammatory rather than an anti-inflammatory effect on human T-cells (Lee et al, 2018).…”

Effects of dexmedetomidine on the function of distal organs and oxidative stress after lower limb ischaemia–reperfusion in elderly patients undergoing unilateral knee arthroplasty

“…6 In addition, Dex also promotes the release of acetylcholine (Ach) and increases parasympathetic activation, thereby inhibiting the excitability of the central nervous system, 7 and regulates the immune system by dampening the T-cell and natural killer cell response. 8,9 Furthermore, Dex exerts protective effects on vital organs during IRI previously reported by our group 7,10,11 and by others. [12][13][14] To our knowledge, most evidence arises from preclinical experiments, and the association of Dex in remote organ dysfunction following lower limb IRI is less reported.…”

“…This is likely to be implicated in blocking the aggregation of inflammatory cells in the nerve system, reducing neuronal injury caused by the immune response and the incidence of surgical complications such as the stress response and postoperative cognitive impairment 6 . In addition, Dex also promotes the release of acetylcholine (Ach) and increases parasympathetic activation, thereby inhibiting the excitability of the central nervous system, 7 and regulates the immune system by dampening the T‐cell and natural killer cell response 8,9 . Furthermore, Dex exerts protective effects on vital organs during IRI previously reported by our group 7,10,11 and by others 12–14 .…”

Dexmedetomidine Exerts an Anti-inflammatory Effect via α2 Adrenoceptors to Prevent Lipopolysaccharide-induced Cognitive Decline in Mice

“…30 Because α 2 adrenoceptors are present on circulating and tissue immunocytes, 31 dexmedetomidine affects the innate immune response to stressors. 32 Furthermore, because of the imidazole-ringed structure of dexmedetomidine, it has activity at the imidazoline receptor 33 capable of mediating a cholinergic-induced resolution of the innate immune response. 15,34 Dexmedetomidine is a neuroprotectant both clinically 35 and preclinically 36 ; therefore, dexmedetomidine may mitigate cognitive decline through its neuroprotective properties.…”