Chronic infusion of interleukin 1 induces hyperlactatemia and altered regulation of lactate metabolism in skeletal muscle.
Chronic infusion of interleukin 1 induces hyperlactatemia and altered regulation of lactate metabolism in skeletal muscle.
复制标题
DOI：
10.1177/0148607199023004213
复制
发表时间：
1999-07
期刊：
影响因子：
--
通讯作者：
T. Vary;P. O'Neill;R. Cooney;G. Maish;M. Shumate
中科院分区：
文献类型：
--
作者：
T. Vary;P. O'Neill;R. Cooney;G. Maish;M. Shumate
背景：高乳酸血症常见于严重炎症综合征或败血症患者。血浆乳酸浓度升高可能是由细胞因子介导的负责乳酸稳态的特定器官系统的改变引起的。通过观察正常大鼠连续输注白细胞介素1 （IL-1）的后果，探讨IL-1在诱导高乳酸血症和骨骼肌及肝脏乳酸代谢紊乱中的作用。方法雄性Sprague-Dawley大鼠麻醉，颈静脉置管。让大鼠恢复48小时，随后注射生理盐水（对照组）或人重组il -1 α（20微克/千克/天），持续6天。第6天，提取血浆、肝脏和肌肉样品，测定乳酸和丙酮酸脱氢酶（PDH）活性。结果两组患者血浆葡萄糖浓度无显著差异。与对照组相比，IL-1输注导致血浆乳酸浓度增加两倍（p < 0.05）。IL-1输注也导致骨骼肌乳酸含量升高（p < 0.05），而肝脏乳酸含量无升高。与对照组相比，注入IL-1的动物骨骼肌中活性形式的PDH （PDHa）比例显著降低（p < 0.05）。与肌肉相比，肝脏PDHa在两组之间没有差异。肝脏和骨骼肌的总PDH复合物活性均未受影响。结论：IL-1输注导致高乳酸血症，骨骼肌乳酸增加，骨骼肌PDHa降低。我们得出结论，IL-1是骨骼肌乳酸代谢紊乱的潜在介质，而不是肝脏。
BACKGROUND Hyperlactatemia is observed commonly in patients with severe inflammation syndrome or sepsis. Elevated plasma lactate concentrations may be caused by cytokine-mediated alterations in specific organ systems responsible for lactate homeostasis. The role of interleukin 1 (IL-1) in inducing hyperlactatemia and derangements in skeletal muscle and hepatic lactate metabolism was investigated by examining the consequences of infusing IL-1 continuously into normal rats. METHODS Male Sprague-Dawley rats were anesthetized, and catheters were placed in the jugular vein. Rats were allowed to recover for 48 hours and were infused subsequently with either saline (control) or human recombinant IL-1alpha (20 microg/kg/d) for 6 days. On day 6, plasma, liver, and muscle samples were extracted and assayed for lactate and pyruvate dehydrogenase (PDH) activity. RESULTS Plasma glucose concentrations were not different in the two groups. IL-1 infusion resulted in a twofold (p < .05) increase in the plasma lactate concentration compared with controls. IL-1 infusion also resulted in an elevated lactate content in skeletal muscle (p < .05) but not in liver. The proportion of PDH in the active form (PDHa) was reduced significantly (p < .05) in the skeletal muscle of animals infused with IL-1 compared with controls. In contrast to muscle, hepatic PDHa did not differ between the two groups. Total PDH complex activity was not affected in either liver or skeletal muscle. CONCLUSIONS IL-1 infusion results in hyperlactatemia, increased skeletal muscle lactate, and a reduced PDHa in skeletal muscle. We conclude that IL-1 is a potential mediator of the derangements in lactate metabolism in skeletal muscle but not in liver.