Tumor necrosis factor antagonism normalizes rapid eye movement sleep in alcohol dependence.
Title | Tumor necrosis factor antagonism normalizes rapid eye movement sleep in alcohol dependence. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Irwin MR, Olmstead R, Valladares EM, Breen ECrabb, Ehlers CL |
Journal | Biol Psychiatry |
Volume | 66 |
Issue | 2 |
Pagination | 191-5 |
Date Published | 2009 Jul 15 |
ISSN | 1873-2402 |
Keywords | Adult, Alcoholism, Cross-Over Studies, Double-Blind Method, Etanercept, Female, Humans, Immunoglobulin G, Immunologic Factors, Male, Polysomnography, Receptors, Tumor Necrosis Factor, Sleep, REM, Temperance, Tumor Necrosis Factors |
Abstract | 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. |
DOI | 10.1016/j.biopsych.2008.12.004 |
Alternate Journal | Biol. Psychiatry |
PubMed ID | 19185287 |
PubMed Central ID | PMC2761725 |
Grant List | AA 13239 / AA / NIAAA NIH HHS / United States AG 026364 / AG / NIA NIH HHS / United States CA 10014152 / CA / NCI NIH HHS / United States CA116778 / CA / NCI NIH HHS / United States HL 079955 / HL / NHLBI NIH HHS / United States M01 RR000865 / RR / NCRR NIH HHS / United States M01 RR000865-310740 / RR / NCRR NIH HHS / United States M01 RR000865-320782 / RR / NCRR NIH HHS / United States M01 RR000865-328456 / RR / NCRR NIH HHS / United States P30 AG028748 / AG / NIA NIH HHS / United States P30 AG028748-049004 / AG / NIA NIH HHS / United States P30-AG028748 / AG / NIA NIH HHS / United States R01 AA013239 / AA / NIAAA NIH HHS / United States R01 AA013239-06 / AA / NIAAA NIH HHS / United States R01 AG026364 / AG / NIA NIH HHS / United States R01 DA016541 / DA / NIDA NIH HHS / United States R01 DA016541-04 / DA / NIDA NIH HHS / United States RR00827 / RR / NCRR NIH HHS / United States T32 MH019925 / MH / NIMH NIH HHS / United States T32 MH019925-12 / MH / NIMH NIH HHS / United States T32-MH19925 / MH / NIMH NIH HHS / United States |