This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vgontzas, A. N. Articles by Chrousos, G. P. Search for Related Content PubMed PubMed Citation Articles by Vgontzas, A. N. Articles by Chrousos, G. P.

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.

This article has been cited by other articles:

				S. D. Paredes, A. M{a} Marchena, I. Bejarano, J. Espino, C. Barriga, R. V. Rial, R. J. Reiter, and A. B. Rodriguez Melatonin and Tryptophan Affect the Activity-Rest Rhythm, Core and Peripheral Temperatures, and Interleukin Levels in the Ringdove: Changes With Age J Gerontol A Biol Sci Med Sci, March 1, 2009; 64A(3): 340 - 350. [Abstract] [Full Text] [PDF]

				M G Perry, J R Kirwan, D S Jessop, and L P Hunt Overnight variations in cortisol, interleukin 6, tumour necrosis factor {alpha} and other cytokines in people with rheumatoid arthritis Ann Rheum Dis, January 1, 2009; 68(1): 63 - 68. [Abstract] [Full Text] [PDF]

				M. Zarkovic, S. Ignjatovic, M. Dajak, J. Ciric, B. Beleslin, S. Savic, M. Stojkovic, P. Bulat, and B. Trbojevic Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans Eur. J. Endocrinol., November 1, 2008; 159(5): 649 - 652. [Abstract] [Full Text] [PDF]

				T. Liukkonen, P. Rasanen, A. Ruokonen, J. Laitinen, J. Jokelainen, M. Leinonen, V. B. Meyer-Rochow, and M. Timonen C-reactive protein Levels and Sleep Disturbances: Observations Based on The Northern Finland 1966 Birth Cohort Study Psychosom Med, October 1, 2007; 69(8): 756 - 761. [Abstract] [Full Text] [PDF]

				C. A. Hoppmann and P. L. Klumb Daily Goal Pursuits Predict Cortisol Secretion and Mood States in Employed Parents With Preschool Children Psychosom Med, November 1, 2006; 68(6): 887 - 894. [Abstract] [Full Text] [PDF]

				E. M. Friedman, M. S. Hayney, G. D. Love, H. L. Urry, M. A. Rosenkranz, R. J. Davidson, B. H. Singer, and C. D. Ryff Social relationships, sleep quality, and interleukin-6 in aging women PNAS, December 20, 2005; 102(51): 18757 - 18762. [Abstract] [Full Text] [PDF]

				E. O. Bixler, A. N. Vgontzas, H.-M. Lin, S. L. Calhoun, A. Vela-Bueno, and A. Kales Excessive Daytime Sleepiness in a General Population Sample: The Role of Sleep Apnea, Age, Obesity, Diabetes, and Depression J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4510 - 4515. [Abstract] [Full Text] [PDF]

				S. Alesci, P. E. Martinez, S. Kelkar, I. Ilias, D. S. Ronsaville, S. J. Listwak, A. R. Ayala, J. Licinio, H. K. Gold, M. A. Kling, et al. Major Depression Is Associated with Significant Diurnal Elevations in Plasma Interleukin-6 Levels, a Shift of Its Circadian Rhythm, and Loss of Physiological Complexity in Its Secretion: Clinical Implications J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2522 - 2530. [Abstract] [Full Text] [PDF]

				P. Y. Liu, S. M. Pincus, D. M. Keenan, F. Roelfsema, and J. D. Veldhuis Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R440 - R446. [Abstract] [Full Text] [PDF]

				A. N. Vgontzas, E. Zoumakis, E. O. Bixler, H.-M. Lin, H. Follett, A. Kales, and G. P. Chrousos Adverse Effects of Modest Sleep Restriction on Sleepiness, Performance, and Inflammatory Cytokines J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2119 - 2126. [Abstract] [Full Text] [PDF]

				C. F. Hatfield, J. Herbert, E. J. W. van Someren, J. R. Hodges, and M. H. Hastings Disrupted daily activity/rest cycles in relation to daily cortisol rhythms of home-dwelling patients with early Alzheimer's dementia Brain, May 1, 2004; 127(5): 1061 - 1074. [Abstract] [Full Text] [PDF]

				G. P. Chrousos Is 11{beta}-hydroxysteroid dehydrogenase type 1 a good therapeutic target for blockade of glucocorticoid actions? PNAS, April 27, 2004; 101(17): 6329 - 6330. [Full Text] [PDF]

				I. A. Harsch, S. P. Schahin, M. Radespiel-Troger, O. Weintz, H. Jahreiss, F. S. Fuchs, G. H. Wiest, E. G. Hahn, T. Lohmann, P. C. Konturek, et al. Continuous Positive Airway Pressure Treatment Rapidly Improves Insulin Sensitivity in Patients with Obstructive Sleep Apnea Syndrome Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 156 - 162. [Abstract] [Full Text] [PDF]

				C. Otte, A. Yassouridis, H. Jahn, P. Maass, N. Stober, K. Wiedemann, and M. Kellner Mineralocorticoid Receptor-Mediated Inhibition of the Hypothalamic-Pituitary-Adrenal Axis in Aged Humans J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2003; 58(10): B900 - 905. [Abstract] [Full Text] [PDF]