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Influence of endotoxin on nocturnal sleep in humans
Abstract
Sleepiness is a common complaint during infectious diseases, but the interaction between sleep and host defense mechanisms has been poorly explored in humans. We therefore studied the effect of endotoxin, a major pathophysiological factor in gram-negative bacterial infections, on sleep and on parameters of the primary host response in men. In a single-blind counterbalanced trial, 15 healthy volunteers received either placebo or Salmonella abortus equi endotoxin (0.4 ng/kg body wt) intravenously on two separate occasions. Nocturnal sleep was recorded, and rectal temperature and the plasma levels of tumor necrosis factor-alpha, interleukin-6, adrenocorticotropic hormone, and cortisol were monitored for 12 h. Endotoxin reduced the relative amounts of wakefulness (P < 0.05) and rapid-eye-movement (REM) sleep (P < 0.05) and increased the relative amount of non-REM sleep (P < 0.01). Electroencephalogram delta power during non-REM sleep, as measured by spectral analysis, was not altered by endotoxin. The endotoxin-induced changes in sleep structure were related temporally and quantitatively to the increases in rectal temperature and to the release of cytokines and neurohormones. It is concluded that cytokines and neurohormones mediate the effects of endotoxin upon sleep. The ensuing increase in non-REM sleep may be part of the adaptive host response to bacterial infections in humans.
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“in humans, NREM sleep enhancing or intensifying effects are restricted to times of very mild host response activation, whereas stronger responses characterized by large cytokine increases and fever caused sleep disruption (224, 396, 442).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [442]
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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
Freedman, N. S., Gazendam, J. A. C., LEVAN, L., Pack, A. I., & Schwab, R. J. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.163.2.9912128 · Cited by 695
Mullington, J. M., Simpson, N. S., Meier-Ewert, H. K., & Haack, M. (2010) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.08.014 · Cited by 519
Shearer, W. T., Reuben, J. M., Mullington, J. M., Price, N. J., Lee, B.-N., Smith, E. O., Szuba, M. P., Van Dongen, H. P. A., & Dinges, D. F. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.112270 · Cited by 455
Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis
Beishuizen, A., & THIJS, L. G. (2003) · Journal of Endotoxin Research · doi:10.1179/096805103125001298 · Cited by 337
Metadata
- Authors
- Pollmacher, T., Schreiber, W., Gudewill, S., Vedder, H., Fassbender, K., Wiedemann, K., Trachsel, L., Galanos, C., & Holsboer, F.
- Affiliations
- Max Planck Institute of Psychiatry, Department of Psychiatry, Munich, Federal Republic of Germany.
- Max Planck Institute of Psychiatry (DE)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 1993-06-01
- Volume
- 264
- Issue
- 6
- Pages
- R1077-R1083
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W1899504327
- Cited by
- 119
- References
- 0
- Citations by year
- 2025: 4 · 2024: 5 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 10 · 2014: 2 · 2013: 4 · 2012: 2
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- endotoxin, Salmonella abortus equi, nocturnal sleep, sleep architecture, REM sleep, NREM sleep, wakefulness, cytokines, TNF-α, interleukin-6, ACTH, cortisol, body temperature, host defense, gram-negative bacterial infection, sleepiness
- MeSH terms
- Adrenocorticotropic Hormone, Adult, Body Temperature, Endotoxins, Humans, Hydrocortisone, Male, Rectum, Salmonella, Sleep, Sleep Stages, Tumor Necrosis Factor-alpha, Interleukin-6
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