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Disordered Sleep, Nocturnal Cytokines, and Immunity in Alcoholics

From the Department of Psychiatry (L.R.), University of California, San Diego, La Jolla, California; Cousins Center for Psychoneuroimmunonology (J.D., M.I.), Department of Psychiatry and Biobehavioral Sciences and Neuropsychiatric Institute, University of California, Los Angeles; and Department of Psychiatry (M.H.), University of Pittsburgh, Pittsburgh, Pennsylvania.

Address reprint requests to: Michael Irwin, MD, Norman Cousins Professor, Department of Psychiatry and Biobehavioral Sciences, Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, 300 UCLA Medical Plaza, Suite 3-109, Los Angeles CA 90095-7057. Email: mirwin1{at}ucla.edu

OBJECTIVE: Alcoholics who are at risk for infectious disease show profound disturbances of sleep along with decrements of cellular immunity. This study examined the relationships between sleep, nocturnal expression of immunoregulatory cytokines, and natural killer (NK) cell activity in alcoholic patients as compared with control subjects.

METHODS: Alcoholic patients (N = 24) and comparison control subjects (N = 23) underwent all-night polysomnography and serial blood sampling at 23:00, 03:00, and 06:30 hours. Stimulated expression of T_H1 (interferon gamma, IFN-), anti-inflammatory/T_H2 (interleukin 10, IL-10), and proinflammatory cytokines (IL-6) was measured along with NK cell activity across the night.

RESULTS: Alcoholic patients showed lower levels of IL-6 production, suppression of the IL-6/IL-10 ratio, and a reduction of NK cell activity, coupled with losses of delta sleep and increases of rapid eye movement sleep, as compared with control subjects. In addition, alcoholics showed a persistent low ratio of IFN-/IL-10 and reduced levels of NK cell activity, whereas controls had increases of these two immune measures across the night. IL-6 also differentially changed in the two groups; alcoholics showed increases and controls had decreases of IL-6 from 03:00 hours to 06:30 hours. At 06:30 hours, rapid eye movement sleep predicted increases of IL-6 and decreases of NK cell activity independent of the relative contribution of age and chronic alcohol consumption. At 23:00 hours before sleep onset, levels of IL-10 predicted subsequent amounts of delta sleep.

CONCLUSIONS: These data further implicate sleep in the regulation of immune function and suggest that disordered sleep contributes to immune alterations in patients with chronic alcoholism. Moreover, the association between awake levels of the anti-inflammatory/T_H2 cytokine IL-10 and subsequent amounts of delta sleep support the notion of a bidirectional interplay between cytokines and sleep in humans.

Key Words: sleep • immunity • cytokines • natural killer cell activity • alcoholism.

Abbreviations: ANOVA = analysis of variance; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, fourth edition; EEG = electroencephalogram; E:T = effector to target (ratio); IFN- = interferon gamma; IL = interleukin; NK = natural killer; REM = rapid eye movement; T_H = T helper cell.

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