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Disordered Sleep, Nocturnal Cytokines, and Immunity in Alcoholics

Laura Redwine, PhD, Jeff Dang, MPH, Martica Hall, PhD and Michael Irwin, MD

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.



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Fig. 1. Concanavalin-A–stimulated production of IL-10 by peripheral blood mononuclear cells in control ({circ}) and alcoholic (•) African American subjects. Data are presented as mean ± SEM. Blood was drawn at 23:00, 03:00, and 06:30 hours. There was a time effect (F(1,21) = 3.2, p = .05) but no group effect or group by time interaction. Post hoc comparisons revealed significant (p < .05) increases of IL-10 from 23:00 to 03:00 hours in both groups; levels at 03:00 and 06:30 hours were similar.

 


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Fig. 2. Concanavalin-A–stimulated production of TH1 and TH2 cytokines by peripheral blood mononuclear cells in control ({circ}) and alcoholic (•) African American subjects. The ratio of the TH1 to TH2 was determined by dividing the TH1 cytokine IFN-{gamma} by the TH2 cytokine IL-10. A sig-nificant group by time interaction was found (F(2,42) = 4.1, p < .02). The TH1/TH2 ratio increased from 03:00 to 06:30 hours (p < .01) in the controls, whereas the IFN-{gamma}/IL-10 ratio decreased from 23:00 to 03:00 hours (p < .05) and remained low from 03:00 to 06:30 hours in the alcoholics.

 


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Fig. 3. Concanavalin-A–stimulated production of IL-6 by peripheral blood mononuclear cells in control ({circ}) and alcoholic (•) African American subjects. Data are presented as mean ± SEM. Blood was drawn at 23:00, 03:00, and 06:30 hours. There was a significant group effect (F(1,21) = 6.9, p < .01), a significant time effect (F(2,42) = 5.0, p < .01), and a significant group by time interaction (F(2,42) = 5.7, p < .01). IL-6 levels decreased from 03:00 to 06:30 hours (p < .05) in the controls, whereas IL-6 increased from 03:00 to 06:30 hours (p < .01) in alcoholics.

 


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Fig. 4. NK cell activity in African American controls ({circ}) and alcoholics (•). Data are presented as mean ± SEM percentage of specific cytotoxicity at the 20:1 E:T ratio. For NK cell activity, there was a group effect (F(1,39) = 5.6, p < .02) and a time effect (F(2,78) = 3.0, p < .05), but no group by time interaction. In the controls, there was a significant increase of NK cell activity from 23:00 to 06:30 hours (p < .05); the alcoholics showed no change across the nocturnal period.

 


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Fig. 5. Relation between REM sleep (minutes) and concanavalin-A–stimulated production of IL-6 by peripheral blood mononuclear cells at 6:30 hours in control ({circ}) and alcoholic (•) African American subjects. In the total sample, amount of REM sleep was positively correlated with expression of IL-6 at 06:30 hours (Spearman {rho} = 0.45, p < .05).

 


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Fig. 6. Relation between delta sleep (minutes) and concanavalin-A–stimulated production of IL-10 by peripheral blood mononuclear cells at 23:00 hours in control ({circ}) and alcoholic (•) African American subjects. In the total sample, expression of IL-10 at 23:00 hours was positively correlated with delta sleep amounts (Spearman {rho} = 0.46, p < .05).

 





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