Tumor Necrosis Factor Antagonism Normalizes Rapid Eye Movement Sleep in Alcohol Dependence
Tumor Necrosis Factor Antagonism Normalizes Rapid Eye Movement Sleep in Alcohol Dependence
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DOI：
10.1016/j.biopsych.2008.12.004
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发表时间：
2009-07-15
影响因子：
10.6
通讯作者：
Ehlers, Cindy L.
中科院分区：
文献类型：
--
作者：
Irwin, Michael R.;Olmstead, Richard;Ehlers, Cindy L.
背景资料：在酒精依赖中，炎症标志物与快速眼动（REM）睡眠的增加有关，这被认为是酒精复发的预后指标。本研究进行测试是否封锁的生物活性肿瘤坏死因子-α（TNF-α）正常REM睡眠在酒精依赖adultes.Methods：在一项随机，安慰剂对照，双盲，交叉试验，18禁欲酒精依赖的男性成年人接受了单剂量的依那西普（25毫克）与安慰剂的平衡顺序。多导睡眠测量在基线和3个晚上后，依那西普或安慰剂的急性剂量。结果：与安慰剂相比，依那西普的管理产生显着下降的REM睡眠的数量和百分比。快速眼动睡眠的减少是稳健的，并且接近通常在年龄相当的对照受试者中发现的低水平。个体差异的生物活性药物作为指标的循环水平的可溶性肿瘤坏死因子受体II与REM sleep.Conclusions的百分比呈负相关：药理学中和TNF-α活性与显着减少REM睡眠戒酒酒精依赖患者。这些数据表明，TNF-α的循环水平可能在人类REM睡眠的调节中具有生理作用。
Background: In alcohol dependence, markers of inflammation are associated with increases in rapid eye movement (REM) sleep, which is thought to be a prognostic indicator of alcohol relapse. This study was undertaken to test whether blockade of biologically active tumor necrosis factor-alpha (TNF-alpha) normalizes REM sleep in alcohol-dependent adults.Methods: In a randomized, placebo-controlled, double-blind, crossover trial, 18 abstinent alcohol-dependent male adults received a single dose of etanercept (25 mg) versus placebo in a counterbalanced order. Polysomnographic sleep was measured at baseline and for 3 nights after the acute dose of etanercept or placebo.Results: Compared with placebo, administration of etanercept produced significant decreases in the amount and percentage of REM sleep. Decreases in REM sleep were robust and approached low levels typically found in age-comparable control subjects. Individual differences in biologically active drug as indexed by circulating levels of soluble tumor necrosis factor receptor II negatively correlated with the percentage of REM sleep.Conclusions: Pharmacologic neutralization of TNF-alpha activity is associated with significant reductions in REM sleep in abstinent alcohol-dependent patients. These data suggest that circulating levels of TNF-alpha may have a physiologic role in the regulation of REM sleep in humans.