Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple interactions and disturbances in sleep disorders
Abstract
Sleep is an important component of mammalian homeostasis, vital for survival. Sleep disorders are common in the general population and are associated with significant medical, psychologic, and social disturbances. Sleep, in particular deep sleep, has an inhibitory influence on the HPA axis, whereas activation of the HPA axis or administration of glucocorticoids can lead to arousal and sleeplessness. Insomnia, the most common sleep disorder, is associated with a 24-hour increase of ACTH and cortisol secretion, consistent with a disorder of central nervous system hyperarousal. Sleepiness and fatigue are very prevalent in the general population, and recent studies have demonstrated that the proinflammatory cytokines IL-6 and/or TNF-alpha are elevated in disorders associated with excessive daytime sleepiness, such as sleep apnea, narcolepsy, and idiopathic hypersomnia. Sleep deprivation leads to sleepiness and daytime hypersecretion of IL-6. Combined, these findings suggest that the HPA axis stimulates arousal, while IL-6 and TNF-alpha are possible mediators of excessive daytime sleepiness in humans.
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Insomnia may be associated with increased activity in the hypothalamic-pituitary-adrenal axis, which could impair glucose metabolism, particularly in those whose metabolism is already compromised.
“Insomnia may be associated with increased activity in the hypothalamic-pituitary-adrenal axis (22), which could impair glucose metabolism, particularly in those whose metabolism is already compromised.”
From Cross-Sectional Associations Between Measures of Sleep and Markers of Glucose Metabolism Among Subjects With and Without Diabetes (2011) · cites this paper as [22]
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IL-6 and its circadian secretion in humans
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Self-citationIncidence of Diabetes in Middle-Aged Men Is Related to Sleep Disturbances
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Sleep Symptoms Predict the Development of the Metabolic Syndrome
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Links between the innate immune system and sleep
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Obesity and sleep disturbance: The chicken or the egg?
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Restorative sleep predicts the resolution of chronic widespread pain: Results from the EPIFUND study
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Self-citationSleep and the affective response to stress and pain
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Sleep duration and metabolic syndrome in adult populations: a meta-analysis of observational studies
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Sleep Abnormalities in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Review
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Sleep, cognition and cortisol in addison’s disease: a mechanistic relationship
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Sleep Loss and Partner Violence Victimization
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- Authors
- Vgontzas, A. N., & Chrousos, G. P.
- Affiliations
- Pennsylvania State University (US)
- National Institutes of Health (US)
- Corresponding author
- Vgontzas, Alexandros N.
- Venue
- Endocrinology and Metabolism Clinics of North America
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 31
- Issue
- 1
- Pages
- 15-36
- ISSN
- 0889-8529 (ISSN-L)
- OpenAlex
- W2015417570
- Semantic Scholar
- 5d1e4bd4ec259d283345c7551fd5e4c284ccacab
- Cited by
- 414
- References
- 88
- Citations by year
- 2026: 16 · 2025: 30 · 2024: 22 · 2023: 12 · 2022: 22 · 2021: 16 · 2020: 5 · 2019: 13 · 2018: 14 · 2017: 10 · 2016: 13 · 2015: 18 · 2014: 26 · 2013: 25 · 2012: 19
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology and Metabolism Clinics of North America (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- sleep disorders, hypothalamic-pituitary-adrenal axis, cytokines, interleukin-6, TNF-α, insomnia, excessive daytime sleepiness, sleep deprivation, sleep apnea, narcolepsy, idiopathic hypersomnia, glucocorticoids, ACTH, cortisol, hyperarousal, inflammation
- MeSH terms
- Adrenal Glands, Adrenocorticotropic Hormone, Circadian Rhythm, Corticotropin-Releasing Hormone, Glucocorticoids, Humans, Hypothalamus, Pituitary Gland, Sleep, Sleep Wake Disorders, Stress, Physiological, Cytokines
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