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Effects of Sleep on the Production of Cytokines in Humans

Uthgenannt, Dirk MD; Schoolmann, Detlef MD; Pietrowsky, Reinhard PHD; Fehm, Horst-Lorenz MD; Born, Jan PhD

Original Article

The restorative functions of sleep may affect immunologic functioning.The present study examined the effects of sleep on stimulated cytokine release in 13 healthy men. The subjects spent 2 experimental nights in the sleep laboratory. In one condition, lights were turned off at 11:00 PM to enable sleep for 3.5 hours. Thereafter, they stayed awake till 7:00 AM. In the other condition, conversely, subjects stayed awake between 11:00 PM and 3:00 AM. Then, lights were turned off for a 3.5-hour phase of sleep. Blood was sampled every 30 minutes between 11:00 PM and 7:00 AM. Sleep was monitored by polysomnographic recordings. Release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) was determined after stimulation of mononuclear cells with lipopolysaccharide from Escherichia coli. The release of IL-2 was stimulated with phytohe-magglutinin. Compared with wakefulness, after 3 hours of sleep, production of TNF-alpha and IL-1beta was substantially diminished (p <.01). Production of IL-2 was enhanced during sleep (p <.05), with this effect being limited to the second nocturnal sleep phase after 3:00 AM. Sleep-dependent changes in stimulated cytokine release were independent of changes in plasma cortisol concentrations. These results indicate a specific reducing effect of sleep (vs. wakefulness) on cytokine production by monocytes (TNF-alpha and IL-1beta). The rather slow development of the effects calls for further studies to establish the exact time course of the influence of sleep on cytokine production.

From the Departments of Internal Medicine (D.U., H.L.F.) and Clinical Neuroendocrinology (D.S., R.P., J.B.), University of Lubeck, Lubeck, Germany.

Address reprint requests to: Dr. Jan Born, Klinische Forscher-gruppe, Klinische Neuroendokrinologie, Medizinische Universitat zu Lubeck, Haus 23 a, Ratzeburger Allee 160, 23538 Lubeck, FRG.

Received for publication August 6, 1993; revision received April 25, 1994.

Copyright © 1995 by American Psychosomatic Society
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