Effects of Sleep on the Production of Cytokines in Humans

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Abstract
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.