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Impaired Nighttime Sleep in Healthy Old Versus Young Adults Is Associated with Elevated Plasma Interleukin-6 and Cortisol Levels: Physiologic and Therapeutic Implications

Sleep Research and Treatment Center (A.N.V., E.O.B., A.V.-B., A.K.), Department of Psychiatry, and Health Evaluation Sciences (H.-M.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; Pediatric and Reproductive Endocrinology Branch (M.Z., G.P.C.), National Institutes of Health, Bethesda, Maryland 20892; Department of Psychiatry and Biobehavioral Sciences (P.P.), University of California, Los Angeles, California 90095

Address all correspondence and requests for reprints to: Alexandros N. Vgontzas, M.D., Department of Psychiatry H073, Penn State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033. E-mail: axv3{at}psu.edu.

IL-6 and TNF secretion is increased by sleep loss or restriction. IL-6 secretion progressively increases with age, yet its association with decreased quality and quantity of sleep in old adults is unknown. This study examined the alteration of 24-h secretory pattern of IL-6, TNF, and cortisol in 15 young and 13 old normal sleepers who were recorded in the sleep laboratory for four consecutive nights. Serial 24-h plasma measures of IL-6, TNF, and cortisol were obtained during the fourth day, and daytime sleepiness was assessed with the multiple sleep latency test. Old adults, compared with young subjects, slept poorly at night (wake time and percentage stage 1 sleep were increased, whereas their percentage slow wave sleep and percentage sleep time were decreased, P < 0.05). Accordingly, their daytime sleep latency was longer than in young adults (P < 0.05). The mean 24-h IL-6 and cortisol levels were significantly higher in old than young adults (P < 0.05). In both groups, IL-6 and cortisol plasma concentrations were positively associated with total wake time, with a stronger association of IL-6 and cortisol with total wake time in the older individuals (P < 0.05); their combined effect was additive. IL-6 had a negative association with rapid eye movement (REM) sleep only in the young (P < 0.05), but cortisol was associated negatively with REM sleep both in the young and old, with a stronger effect in the young. We conclude that in healthy adults, age-related alterations in nocturnal wake time and daytime sleepiness are associated with elevations of both plasma IL-6 and cortisol concentrations, but REM sleep decline with age is primarily associated with cortisol increases.

Part of this study was presented at the 83rd Annual Meeting of The Endocrine Society, Denver, Colorado, 2001.

Abbreviations: BMI, Body mass index; HPA, hypothalamic-pituitary-adrenal; MMPI, Multiple Minnesota Personality Inventory; REM, rapid eye movement; SL, sleep latency; ST, sleep time; SWS, slow-wave sleep; TWT, total wake time; WTASO, sleep maintenance wake time after sleep onset.

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