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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
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“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
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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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