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腺苷治疗可减弱健康志愿者体内细胞因子白细胞介素-6 对内毒素刺激的反应。

Adenosine treatment attenuates cytokine interleukin-6 responses to endotoxin challenge in healthy volunteers.

作者信息

Soop Anne, Johansson Cecilia, Hjemdahl Paul, Kristiansson Marianne, Gyllenhammar Hans, Li Nailin, Sollevi Alf

机构信息

Department of Anaesthesiology and Intensive Care, Center for Surgical Sciences, Huddinge University Hospital, Stockholm, Sweden.

出版信息

Shock. 2003 Jun;19(6):503-7. doi: 10.1097/01.shk.0000051756.08171.11.

Abstract

Anti-inflammatory effects of adenosine were evaluated in two randomized, double-blind, placebo-controlled studies. In one study healthy male volunteers received no endotoxin (adenosine study, n = 10), in the other intravenous endotoxin (4 ng/kg, endotoxin study n = 11) was given. All subjects were treated with adenosine infusion (40 microg/kg/min) and placebo (saline) infusion in a crossover design. Heart rate, body temperature, blood pressure and plasma cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, IL-10, and soluble TNF receptors I and II), nitric oxide oxidation products, nitrite and nitrate, as well as superoxide anions were determined. There were no significant changes of any measured parameter after adenosine treatment alone. Endotoxin elicited clinical signs of an inflammatory reaction, prominent release of all cytokines and O2- synthesis by neutrophils (N-formyl-methionin-leucyl-phenylalanin-stimulated cells measured by cytochrome C reduction). The plasma IL-6 response to endotoxin was attenuated by adenosine, as IL-6 increased from 0.9 (0.8-1.6) to 1345 (743-1906) pg/mL (median; 25-75th percentiles) with adenosine infusion, and from 0.8 (0.5-1) to 1,959 (1,344-2,505) pg/mL with placebo (P = 0.0065). There was no significant influence of adenosine infusion on the other variables examined. In conclusion, systemic adenosine infusion counteracts the release of IL-6 in healthy volunteers, indicating an anti-inflammatory effect of adenosine which should be further explored.

摘要

在两项随机、双盲、安慰剂对照研究中评估了腺苷的抗炎作用。一项研究中,健康男性志愿者未接受内毒素(腺苷研究,n = 10),另一项研究中给予静脉内毒素(4 ng/kg,内毒素研究,n = 11)。所有受试者采用交叉设计接受腺苷输注(40 μg/kg/min)和安慰剂(生理盐水)输注。测定心率、体温、血压和血浆细胞因子(肿瘤坏死因子 [TNF]-α、白细胞介素 [IL]-6、IL-10以及可溶性TNF受体I和II)、一氧化氮氧化产物、亚硝酸盐和硝酸盐以及超氧阴离子。单独使用腺苷治疗后,任何测量参数均无显著变化。内毒素引发炎症反应的临床体征、所有细胞因子的显著释放以及中性粒细胞的O2-合成(通过细胞色素C还原测定N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸刺激的细胞)。腺苷减弱了血浆IL-6对内毒素的反应,因为腺苷输注时IL-6从0.9(0.8 - 1.6)pg/mL增加至1345(743 - 1906)pg/mL(中位数;第25 - 75百分位数),安慰剂输注时从0.8(0.5 - 1)pg/mL增加至1959(1344 - 2505)pg/mL(P = 0.0065)。腺苷输注对其他检测变量无显著影响。总之,全身性腺苷输注可抵消健康志愿者中IL-6的释放,表明腺苷具有抗炎作用,值得进一步探索。

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