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Microbial Products and Cytokines in Sleep and Fever Regulation
Abstract
Excessive sleepiness and fever are constitutional symptoms associated with systemic infection. Although fevers have been investigated for many years, sleep responses to infectious challenge have only recently been investigated. Inoculation of animals with bacterial, viral, protozoan and fungal organisms result in complex sleep responses dependent upon the microbial agent and route of administration. The general pattern is characterized by an initial robust increase in non-rapid eye movement sleep (NREMS) followed by a period of NREMS inhibition. REMS is inhibited after infectious challenge. The sleep responses are accompanied by fever but the two responses are, in part, independent from each other. Sleep responses, like fevers, may be beneficial to host defense although this area is relatively uninvestigated. Microbial products likely responsible for sleep and fever responses include bacterial muramyl peptides and endotoxin, and viral double stranded RNA. These microbial products induce sleep and fever responses in animal models. The exact mechanism of how these structurally diverse microbial products elicit sleep and fever remain unknown; however these substances share the ability to induce cytokine production. Cytokines such as interleukin-1 (IL-1), tumor necrosis factor, acidic fibroblast growth factor (FGF), and interferon-alpha (IFN-alpha) are somnogenic whether given directly into brain or intravenously. Other cytokines lack somnogenic activity, e.g., IL-2, IL-6, IFN beta and basic FGF. The somnogenic actions of cytokines probably involve growth hormone-releasing hormone (GHRH) and nitric oxide. Anti-GHRH or inhibition of NO production inhibits normal sleep and inhibits IL-1-induced sleep. In conclusion, cytokines are likely key mediators of fever and sleep responses to infection. The microbial-cytokine altered sleep likely results from an amplification of physiological sleep mechanisms which include cytokines, several neuropeptides and neurotransmitters such as nitric oxide.
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From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [302]
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“dsRNA has been shown to induce several cytokines including TNF- and IL-1 in monocytic cell lines (20, 21).”
BackgroundEndoscopic sinus surgery improves cognitive dysfunction in patients with chronic rhinosinusitis
Alt, J. A., Mace, J. C., Smith, T. L., & Soler, Z. M. (2016) · International Forum of Allergy & Rhinology · doi:10.1002/alr.21820 · Cited by 46
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Effects of Sleep on Endotoxin-Induced Host Responses in Healthy Men
Haack, M., Schuld, A., Kraus, T., & Pollmächer, T. (2001) · Psychosomatic Medicine · doi:10.1097/00006842-200107000-00008 · Cited by 44
“The injection time points of placebo and endotoxin in the sleep group (5 minutes after initiation of stable SWS) were 2341 hours 6 13 minutes (range 2325– 0005 hours) and 2349 hours 6 18 minutes (range 2317–0017 hours), respectively (F(1,9) 5 3.”
BackgroundInfluentialBiological properties of bacterial peptidoglycan
Johannsen, L. (1993) · Apmis · doi:10.1111/j.1699-0463.1993.tb00119.x · Cited by 44
Spontaneous, homeostatic, and inflammation-induced sleep in NF-κB p50 knockout mice
Jhaveri, K. A., Ramkumar, V., Trammell, R. A., & Toth, L. A. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00262.2006 · Cited by 40
“LPS also activates NF- B (46), which in turn promotes the production of TNF- , IL-1 , and NOS (16, 62).”
BackgroundInfluentialA Review of Sleep in Selected Immune and Autoimmune Disorders
Lashley, F. R. (2003) · Holistic Nursing Practice · doi:10.1097/00004650-200303000-00002 · Cited by 47
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“, 1982), the idea has been around for a long time that pro-inflammatory cytokines that are released in response to microbial challenge are involved in the homeostatic regulation of sleep, especially of slow wave sleep (SWS) (Krueger and Majde, 1994; Krueger et al., 1995).”
Background
Metadata
- Authors
- Krueger, J. M., & Majde, J. A.
- Affiliations
- University of Tennessee Health Science Center (US)
- Office of Naval Research (US)
- Venue
- Critical Reviews™ in Immunology
- Publisher
- Begell House
- Published
- 1994
- Volume
- 14
- Issue
- 3-4
- Pages
- 355-379
- ISSN
- 0197-3355 (ISSN-L)
- 2162-6472
- OpenAlex
- W2024033128
- Cited by
- 213
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 6 · 2018: 1 · 2017: 4 · 2016: 4 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Critical Reviews in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep regulation, fever regulation, cytokines, microbial products, infection, NREM sleep, REM sleep, interleukin-1, TNF-α, interferon-alpha, acidic fibroblast growth factor, growth hormone-releasing hormone, nitric oxide, muramyl peptides, endotoxin, double-stranded RNA, host defense
- MeSH terms
- Animals, Bacterial Proteins, Endotoxins, Fever, Humans, Models, Biological, RNA, Double-Stranded, Sleep, Viruses, Cytokines
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