Tsigos C, Papanicolaou D A, Kyrou I, Defensor R, Mitsiadis C S, Chrousos G P
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Endocrinol Metab. 1997 Dec;82(12):4167-70. doi: 10.1210/jcem.82.12.4422.
Inflammatory cytokines have metabolic actions that probably contribute to the general adaptation of the organism during infectious or inflammatory stress. To examine the effects of interleukin 6 (IL-6), the main circulating cytokine, on glucose metabolism in man, we performed dose-response studies of recombinant human IL-6 in normal volunteers. Increasing single doses of IL-6 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/Kg BW) were injected sc in 15 healthy male volunteers (3 in each dose) after a 12-h fast. All IL-6 doses were tolerated well and produced no significant adverse effects. We measured the circulating levels of glucose, insulin, C-peptide, and glucagon at baseline and half-hourly over 4 h after the IL-6 injection. Mean peak plasma levels of IL-6 were achieved between 120 and 240 min and were 8, 22, 65, 290, and 4050 pg/mL, respectively, for the 5 doses. After administration of the 2 smaller IL-6 doses, we observed no significant changes in plasma glucose levels, which, because of continued fasting, decreased slightly over time. By 60 min after the 3 higher IL-6 doses, however, the decline in fasting blood glucose was arrested, and glucose levels increased in a dose-dependent fashion. The concurrent levels of plasma insulin and C-peptide were not affected by any IL-6 dose. In contrast, IL-6 caused significant increases in plasma glucagon levels, which peaked between 120 and 150 min after the IL-6 injection. In conclusion, sc IL-6 administration induced dose-dependent increases in fasting blood glucose, probably by stimulating glucagon release and other counteregulatory hormones and/or by inducing peripheral resistance to insulin action.
炎症细胞因子具有代谢作用，这可能有助于机体在感染或炎症应激期间的整体适应。为了研究主要循环细胞因子白细胞介素6（IL-6）对人体葡萄糖代谢的影响，我们在正常志愿者中进行了重组人IL-6的剂量反应研究。15名健康男性志愿者（每个剂量3人）在禁食12小时后，皮下注射递增单剂量的IL-6（0.1、0.3、1.0、3.0和10.0mg/Kg体重）。所有IL-6剂量均耐受性良好，未产生明显不良反应。我们在基线以及IL-6注射后4小时内每半小时测量一次葡萄糖、胰岛素、C肽和胰高血糖素的循环水平。5个剂量的IL-6平均血浆峰值水平在120至240分钟之间达到，分别为8、22、65、290和4050pg/mL。给予较小的2个IL-6剂量后，我们观察到血浆葡萄糖水平无显著变化，由于持续禁食，其随时间略有下降。然而，在给予较高的3个IL-6剂量后60分钟，空腹血糖的下降停止，葡萄糖水平呈剂量依赖性增加。血浆胰岛素和C肽的同时水平不受任何IL-6剂量的影响。相反，IL-6导致血浆胰高血糖素水平显著升高，在IL-6注射后120至150分钟达到峰值。总之，皮下注射IL-6可诱导空腹血糖呈剂量依赖性增加，可能是通过刺激胰高血糖素释放和其他对抗调节激素和/或通过诱导外周对胰岛素作用的抵抗。
