Tumor necrosis factor antagonism normalizes rapid eye movement sleep in alcohol dependence.
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.
Irwin
Michael R
MR
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, University of California, Los Angeles, California 90095-7076, USA. mirwin1@ucla.edu
Olmstead
Richard
R
Valladares
Edwin M
EM
Breen
Elizabeth Crabb
EC
Ehlers
Cindy L
CL
D000328:Adult; D000437:Alcoholism / Q000523:psychology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D008297:Male; D017286:Polysomnography; D018124:Receptors, Tumor Necrosis Factor; D012895:Sleep, REM / Q000187:drug effects*; D013695:Temperance; D000079424:Tumor Necrosis Factor Inhibitors
D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D000079424:Tumor Necrosis Factor Inhibitors; D000068800:Etanercept