Esposito Katherine, Nappo Francesco, Marfella Raffaele, Giugliano Giovanni, Giugliano Francesco, Ciotola Myriam, Quagliaro Lisa, Ceriello Antonio, Giugliano Dario
Department of Geriatric and Metabolic Diseases, Second University of Naples, Italy.
Circulation. 2002 Oct 15;106(16):2067-72. doi: 10.1161/01.cir.0000034509.14906.ae.
Circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are elevated in diabetic patients. We assessed the role of glucose in the regulation of circulating levels of IL-6, TNF-alpha, and interleukin-18 (IL-18) in subjects with normal or impaired glucose tolerance (IGT), as well as the effect of the antioxidant glutathione.
Plasma glucose levels were acutely raised in 20 control and 15 IGT subjects and maintained at 15 mmol/L for 5 hours while endogenous insulin secretion was blocked with octreotide. In control subjects, plasma IL-6, TNF-alpha, and IL-18 levels rose (P<0.01) within 2 hours of the clamp and returned to basal values at 3 hours. In another study, the same subjects received 3 consecutive pulses of intravenous glucose (0.33 g/kg) separated by a 2-hour interval. Plasma cytokine levels obtained at 3, 4, and 5 hours were higher (P<0.05) than the corresponding values obtained during the clamp. The IGT subjects had fasting plasma IL-6 and TNF-alpha levels higher (P<0.05) than those of control subjects. The increase in plasma cytokine levels during the clamping lasted longer (4 hours versus 2 hours, P<0.01) in the IGT subjects than in the control subjects, and the cytokine peaks of IGT subjects after the first glucose pulse were higher (P<0.05) than those of control subjects. On another occasion, 10 control and 8 IGT subjects received the same glucose pulses as above during an infusion of glutathione; plasma cytokine levels did not show any significant change from baseline after the 3 glucose pulses.
Hyperglycemia acutely increases circulating cytokine concentrations by an oxidative mechanism, and this effect is more pronounced in subjects with IGT. This suggests a causal role for hyperglycemia in the immune activation of diabetes.
糖尿病患者循环中的白细胞介素 -6（IL -6）和肿瘤坏死因子 -α（TNF -α）水平升高。我们评估了葡萄糖在糖耐量正常或糖耐量受损（IGT）受试者中对循环中IL -6、TNF -α和白细胞介素 -18（IL -18）水平调节的作用，以及抗氧化剂谷胱甘肽的影响。
在20名对照受试者和15名IGT受试者中急性升高血浆葡萄糖水平，并使用奥曲肽阻断内源性胰岛素分泌的情况下，将其维持在15 mmol/L达5小时。在对照受试者中，钳夹2小时内血浆IL -6、TNF -α和IL -18水平升高（P<0.01），并在3小时恢复至基础值。在另一项研究中，相同受试者接受连续3次静脉注射葡萄糖（0.33 g/kg），间隔2小时。在3、4和5小时测得的血浆细胞因子水平高于钳夹期间相应的值（P<0.05）。IGT受试者的空腹血浆IL -6和TNF -α水平高于对照受试者（P<0.05）。与对照受试者相比，IGT受试者在钳夹期间血浆细胞因子水平升高持续时间更长（4小时对2小时，P<0.01），且IGT受试者在首次葡萄糖脉冲后的细胞因子峰值高于对照受试者（P<0.05）。在另一次实验中，10名对照受试者和8名IGT受试者在输注谷胱甘肽期间接受与上述相同的葡萄糖脉冲；3次葡萄糖脉冲后血浆细胞因子水平与基线相比未显示任何显著变化。
高血糖通过氧化机制急性增加循环细胞因子浓度，且这种作用在IGT受试者中更明显。这表明高血糖在糖尿病免疫激活中起因果作用。
