The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Circadian Interleukin-6 Secretion and Quantity and Depth of Sleep
Abstract
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 post-deprivation 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 under-secretion 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.
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In the citing paper
“Sleep disturbances are associated with alterations in IL-6 (37), and sleep differences between caregivers and controls have frequently been reported (8).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [37]
In the citing paper
“Other researchers have demonstrated that higher plasma IL-6 levels are associated with adverse health habits: values are higher in smokers than nonsmokers, in individuals who report less physical activity, in those whose sleep is impaired, and in those with a higher BMI, all behaviors that are adversely affected by stress (14, 34, 37, 50-52).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [37]
In the citing paper
“and IL-6 (Vgontzas et al, 1999).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Vgontzas et al, 1999
In the citing paper
“total night sleep deprivation diminishes the increase in IL-6 by about half (Vgontzas and Papanicolaou et al, 1999).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Vgontzas and Papanicolaou et al, 1999
In the citing paper
“For circulating concentrations of interleukin (IL)-6, eg, there are two peaks, at 1900 hours and again at 0500 hours, and these peaks appear to be driven by circadian processes (Vgontzas et al, 1999).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Vgontzas et al, 1999
In the citing paper
“There is good evidence that insomnia increases the risk for certain disorders including depression (439), hypertension (31), and type 2 diabetes (561)”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [561]
In the citing paper
“the magnitude of such dysregulations may depend on the presence of objective sleep impairments, which have been suggested as a marker indicating the biological severity and the medical impact of the disorder”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [561]
In the citing paper
“After a night of TSD, mean daytime IL-6 values were significantly higher (p<0.05) than baseline and a nighttime undersecretion (p<0.05) was reported [106].”
From Association between sleep deficiency and cardiometabolic disease: implications for health disparities (2016) · cites this paper as [106]
Citations
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The Pathophysiologic Roles of Interleukin-6 in Human Disease
Papanicolaou, D. A., Wilder, R. L., Manolagas, S. C., & Chrousos, G. P. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-128-2-199801150-00009 · Cited by 1,146
Self-citationVgontzas, A. N., Papanicolaou, D. A., Bixler, E. O., Kales, A., Tyson, K., & Chrousos, G. P. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.5.3950 · Cited by 974
Self-citationEffects of sleep and circadian rhythm on human circulating immune cells
Born, J., Lange, T., Hansen, K., Mölle, M., & Fehm, H. L. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.9.4454 · Cited by 611
Ultrashort sleep-waking schedule. III. ‘Gates’ and ‘Forbidden zones’ for sleep
Lavie, P. (1986) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(86)90123-9 · Cited by 480
Späth‐Schwalbe, E. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.5.1573 · Cited by 377
A Healthy Body in a Healthy Mind--and Vice Versa--The Damaging Power of "Uncontrollable" Stress
Chrousos, G. P., & Gold, P. W. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.6.4908 · Cited by 304
Self-citationMojón, A., Fernández, J. R., & Hermida, R. C. (1992) · Chronobiology International · doi:10.3109/07420529209064552 · Cited by 268
Self-citationConcepts and models of sleep regulation: an overview
Borbély, A. A., & Achermann, P. (1992) · Journal of Sleep Research · doi:10.1111/j.1365-2869.1992.tb00013.x · Cited by 250
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Stress and disorders of the stress system
Chrousos, G. P. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.106 · Cited by 3,215
Self-citationIrwin, M. R., Olmstead, R., & Carroll, J. E. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.05.014 · Cited by 2,085
The hyperarousal model of insomnia: A review of the concept and its evidence
Riemann, D., Spiegelhalder, K., Feige, B., Voderholzer, U., Berger, M., Perlis, M., & Nissen, C. (2010) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2009.04.002 · Cited by 1,789
The Sleep-Immune Crosstalk in Health and Disease
Besedovsky, L., Lange, T., & Haack, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00010.2018 · Cited by 1,479
Oxidative stress, insulin signaling, and diabetes
Rains, J., & Jain, S. K. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.12.006 · Cited by 1,468
Metadata
- Authors
- Vgontzas, A. N., Papanicolaou, D. A., Bixler, E. O., Lotsikas, A., Zachman, K., Kales, A., Prolo, P., Wong, M.-L., Licinio, J., Gold, P. W., Hermida, R. C., Mastorakos, G., & Chrousos, G. P.
- Affiliations
- Pennsylvania State University (US)
- National Institutes of Health (US)
- National Institute of Mental Health (US)
- National and Kapodistrian University of Athens (GR)
- Corresponding author
- Vgontzas, Alexandros N.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1999-08
- Volume
- 84
- Issue
- 8
- Pages
- 2603-2607
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2155954337
- Cited by
- 516
- References
- 16
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 29 · 2023: 21 · 2022: 25 · 2021: 17 · 2020: 21 · 2019: 17 · 2018: 11 · 2017: 14 · 2016: 25 · 2015: 28 · 2014: 19 · 2013: 24 · 2012: 17
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- Pennsylvania State University
- University of Pennsylvania Health System
- Penn State College of Medicine
- NIH Clinical Center
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- interleukin-6, circadian rhythm, sleep deprivation, sleep depth, sleep quantity, daytime sleepiness, fatigue, inflammatory cytokines, hypothalamic-pituitary-adrenal axis, sleepiness
- MeSH terms
- Adult, Circadian Rhythm, Humans, Male, Sleep, Sleep Deprivation, Interleukin-6
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