Circadian Interleukin-6 Secretion and Quantity and Depth of Sleep

• Published in: The journal of clinical endocrinology and metabolism Vol. 84; no. 8; pp. 2603 - 2607
• Main Authors: Vgontzas, Alexandros N., Papanicolaou, Dimitris A., Bixler, Edward O., Lotsikas, Angela, Zachman, Keith, Kales, Anthony, Prolo, Paolo, Wong, Ma-Li, Licinio, Julio, Gold, Philip W., Hermida, Ramon C., Mastorakos, George, Chrousos, George P.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.08.1999; Endocrine Society
• Subjects: Adult; Biological and medical sciences; Circadian Rhythm; Circadian rhythms; Cytokines; Daytime; Fatigue; Functional investigation of endocrine glands and genital system; Humans; Hypothalamic-pituitary-adrenal axis; Hypothalamus; Interleukin 6; Interleukin-6 - secretion; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Nighttime; Pituitary; Sleep; Sleep and wakefulness; Sleep Deprivation; Human; Interleukin 6; Somnolence; Sleep stage; Pathophysiology; Hypothalamohypophysoadrenal axis; Cytokine; Sleep disorder; Fatigue; Biosynthesis; Circadian rhythm; Nocturnal variation
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.84.8.5894

Patients with pathologically increased daytime sleepiness and fatigue have elevated levels of circulating interleukin-6 (IL-6). The latter is an inflammatory cytokine, which causes sickness manifestations, including somnolence and fatigue, and activation of the hypothalamic-pituitary-adrenal axis. In this study, we examined: 1) the relation between serial measurements of plasma IL-6 and quantity and depth of sleep, evaluated by polysomnography; and 2) the effects of sleep deprivation on the nyctohemeral pattern of IL-6 secretion. Eight healthy young male volunteers were sampled for 24 h twice, at the baseline state, after a normal night’s sleep and after total overnight sleep deprivation. At the baseline state, IL-6 was secreted in a biphasic circadian pattern with two nadirs at 0800 and 2100 and two zeniths at 1900 and 0500 (P < 0.01). The baseline amount of sleep correlated negatively with the overall daytime secretion of the cytokine (P < 0.05). Also, depth of sleep at baseline correlated negatively with the postdeprivation increase of daytime secretion of IL-6 (P < 0.05). Sleep deprivation changed the temporal pattern of circadian IL-6 secretion but not the overall amount. Indeed, during the postdeprivation period, the mean daytime (0800–2200 h) levels of IL-6 were significantly higher (P < 0.05), whereas the nighttime (2200–0600 h) levels were lower than the predeprivation values. Thus, sleep-deprived subjects had daytime oversecretion and nighttime undersecretion of IL-6; the former might be responsible for their daylong somnolence and fatigue, the latter for the better quality (depth) of their sleep. These data suggest that a good night’s sleep is associated with decreased daytime secretion of IL-6 and a good sense of well-being and that good sleep is associated with decreased exposure of tissues to the proinflammatory and potentially detrimental actions of IL-6. Sleep deprivation increases daytime IL-6 and causes somnolence and fatigue during the next day, whereas postdeprivation decreases nighttime IL-6 and is associated with deeper sleep.