Elevation of Plasma Cytokines in Disorders of Excessive Daytime Sleepiness: Role of Sleep Disturbance and Obesity
Abstract
Excessive daytime sleepiness (EDS) and fatigue are frequent symptoms in the general population and the chief complaint of the majority of patients at Sleep Disorders Centers. There is evidence that the inflammatory cytokines tumor necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1beta), and IL-6 are involved in physiological sleep regulation and that their administration to humans is associated with sleepiness and fatigue. To explore whether plasma levels of TNF alpha, IL-1beta, and IL-6 are elevated in patients with EDS, we measured morning plasma levels of TNF alpha, IL-1beta, and IL-6 in 12 sleep apneics, 11 narcoleptics, 8 idiopathic hypersomniacs, and 10 normal controls. TNF alpha was significantly elevated in sleep apneics and narcoleptics compared to that in normal controls (P < 0.001 and P = 0.001, respectively). Plasma IL-1beta concentrations were not different between sleep disorder patients and controls, whereas IL-6 was markedly and significantly elevated in sleep apneics compared to that in normal controls (P = 0.028). The primary factor influencing TNF alpha values was the degree of nocturnal sleep disturbance, whereas the primary determinant for IL-6 levels was the body mass index. Our findings suggest that TNF alpha and IL-6 might play a significant role in mediating sleepiness and fatigue in disorders of EDS in humans.
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Higher levels of IL-6 are associated with greater body fat and a higher BMI.
“Other researchers have shown that higher levels of IL-6 levels are associated with greater body fat and a higher BMI (34).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [34]
Higher plasma IL-6 levels are associated with adverse health habits: higher in smokers, less physical activity, impaired sleep, higher BMI.
“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 [34]
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- Authors
- Vgontzas, A. N., Papanicolaou, D. A., Bixler, E. O., Kales, A., Tyson, K., & Chrousos, G. P.
- Affiliations
- Pennsylvania State University (US)
- National Institutes of Health (US)
- Corresponding author
- Vgontzas, Alexandros N.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1997-05
- Volume
- 82
- Issue
- 5
- Pages
- 1313-1316
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1975319022
- Cited by
- 974
- References
- 22
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 24 · 2023: 24 · 2022: 32 · 2021: 33 · 2020: 25 · 2019: 24 · 2018: 23 · 2017: 23 · 2016: 29 · 2015: 40 · 2014: 42 · 2013: 38 · 2012: 46
- FWCI
- 11.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- excessive daytime sleepiness, plasma cytokines, TNF-α, IL-1β, interleukin-6, sleep apnea, narcolepsy, idiopathic hypersomnia, sleep disorders, obesity, body mass index, fatigue, inflammation
- MeSH terms
- Adult, Female, Humans, Disorders of Excessive Somnolence, Interleukin-1, Male, Narcolepsy, Obesity, Sleep Apnea Syndromes, Sleep Wake Disorders, Tumor Necrosis Factor-alpha, Interleukin-6, Body Mass Index, Cytokines
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