The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
IL-6 and Its Circadian Secretion in Humans
Abstract
Interleukin-6 (IL-6) is a pleiotropic cytokine produced by numerous types of immune and nonimmune cells and is involved in many pathophysiologic mechanisms in humans. Many studies suggest that IL-6 is a putative ‘sleep factor’ and its circadian secretion correlates with sleep/sleepiness. IL-6 is elevated in disorders of excessive daytime sleepiness such as narcolepsy and obstructive sleep apnea. It correlates positively with body mass index and may be a mediator of sleepiness in obesity. Also the secretion of this cytokine is stimulated by total acute or partial short-term sleep loss reflecting the increased sleepiness experienced by sleep-deprived individuals. Studies that evaluated the 24-hour secretory pattern of IL-6 in healthy young adults suggest that IL-6 is secreted in a biphasic circadian pattern with two nadirs at about 08.00 and 21.00, and two zeniths at about 19.00 and 05.00 h. In contrast, following sleep deprivation or in disorders of sleep disturbance, e.g., insomnia, IL-6 peaks during the day and, based on the level of stress system activity, i.e., cortisol secretion, contributes to either sleepiness and deep sleep (low cortisol) or feelings of tiredness and fatigue and poor sleep (high cortisol). In order to address concerns about the potential impact of differences of IL-6 levels between the beginning and the end of the 24-hour blood-drawing experiment, we proceeded with a cosinor analysis of ‘detrended’ data in young and old healthy individuals. This new analysis did not affect the biphasic circadian pattern of IL-6 secretion in young adults, while it augmented the flattened circadian pattern in old individuals in whom the difference was greater. Finally, IL-6 appears to be somnogenic in rats and exhibits a diurnal rhythm that follows the sleep/wake cycle in these animals. We conclude that IL-6 is a mediator of sleepiness and its circadian pattern reflects the homeostatic drive for sleep.
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“The proinflammatory cytokines IL-1, TNF-α, and IL-6 display a circadian pattern of secretion with peak levels correlating with feelings of sleepiness and sleep onset (Imeri and Opp, 2009; Vgontzas et al., 2005).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Vgontzas et al., 2005
Citations
Cites
Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor-α,in Vivo1
Mohamed‐Ali, V., Goodrick, S., Rawesh, A., Katz, D. R., Miles, J. M., Yudkin, J. S., Klein, S., & Coppack, S. W. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.12.4450 · Cited by 2,032
Manolagas, S. C., & Jilka, R. L. (1995) · New England Journal of Medicine · doi:10.1056/nejm199502023320506 · Cited by 1,670
Vgontzas, A. N., Papanicolaou, D. A., Bixler, E. O., Hopper, K. D., Lotsikas, A. J., LIN, H., Kales, A., & Chrousos, G. P. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.3.6484 · Cited by 1,209
Self-citationThe 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-citationAdverse Effects of Modest Sleep Restriction on Sleepiness, Performance, and Inflammatory Cytokines
Vgontzas, A. N., Zoumakis, E., Bixler, E. O., Lin, H.-M., Follett, H., Kales, A., & Chrousos, G. P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031562 · Cited by 1,050
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-citationVgontzas, A. N., Bixler, E. O., Lin, H.-M., Prolo, P., Mastorakos, G., Vela-Bueno, A., Kales, A., & Chrousos, G. P. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.8.7778 · Cited by 884
Self-citationGirasole, G., Jilka, R. L., Passeri, G., Boswell, S. H., Boder, G. B., Williams, D. C., & Manolagas, S. C. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115668 · Cited by 677
Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans.
Mastorakos, G., Chrousos, G. P., & Weber, J. S. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.77.6.8263159 · Cited by 591
Self-citationCircadian Interleukin-6 Secretion and Quantity and Depth of Sleep
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., et al. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.8.5894 · Cited by 516
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Research works printed but not linked: 11
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- 10.1210%2Fen.137.12.5250 · DOI · Paper page
- 10.1210%2Fjc.85.3.1151 · DOI
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- 10.1210%2Fjc.86.8.3787 · DOI · Paper page
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Steptoe, A., Hamer, M., & Chida, Y. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.03.011 · Cited by 1,278
Manna, P., & Jain, S. K. (2015) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2015.0095 · Cited by 1,211
Pace, T. W. W., Negi, L. T., Adame, D. D., Cole, S. P., Sivilli, T. I., Brown, T. D., Issa, M. J., & Raison, C. L. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.08.011 · Cited by 748
“Because cortisol and IL-6 demonstrate circadian variability (Posener et al., 1996; Vgontzas et al., 2005), we also included time of stressor initiation as a covariate in all analyses of these variables.”
BackgroundInterleukin-6 in Aging and Chronic Disease: A Magnificent Pathway
Maggio, M. G., Guralnik, J. M., Longo, D. L., & Ferrucci, L. (2006) · The Journals of Gerontology Series A · doi:10.1093/gerona/61.6.575 · Cited by 696
Gut microbiome diversity is associated with sleep physiology in humans
Smith, R. P., Easson, C., Lyle, S. M., Kapoor, R., Donnelly, C. P., Davidson, E. J., Parikh, E., Lopez, J. V., & Tartar, J. L. (2019) · PLOS ONE · doi:10.1371/journal.pone.0222394 · Cited by 390
Metadata
- Authors
- Vgontzas, A. N., Bixler, E. O., Lin, H.-M., Prolo, P., Trakada, G., & Chrousos, G. P.
- Affiliations
- Pennsylvania State University (US)
- University of California, Los Angeles (US)
- National Institutes of Health (US)
- Venue
- Neuroimmunomodulation
- Publisher
- S. Karger AG
- Published
- 2005
- Volume
- 12
- Issue
- 3
- Pages
- 131-140
- ISSN
- 1021-7401 (ISSN-L)
- 1423-0216
- OpenAlex
- W1970138464
- Cited by
- 338
- References
- 47
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 10 · 2023: 20 · 2022: 14 · 2021: 7 · 2020: 19 · 2019: 22 · 2018: 12 · 2017: 19 · 2016: 16 · 2015: 14 · 2014: 10 · 2013: 17 · 2012: 20
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImmunoModulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- interleukin-6, circadian rhythm, sleepiness, sleep deprivation, narcolepsy, obstructive sleep apnea, obesity, insomnia, cortisol, aging, cosinor analysis, sleep homeostasis, rats
- MeSH terms
- Aging, Animals, Circadian Rhythm, Homeostasis, Humans, Hydrocortisone, Sleep, Sleep Wake Disorders, Species Specificity, Interleukin-6, Up-Regulation
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