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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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“SWS-dependent processes might actively counteract inflammation in the brain”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [302]
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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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