Cited by 507Sleep and Wakefulness ResearchNeuroinflammation and Neurodegeneration MechanismsCircadian rhythm and melatonin

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The Role of Cytokines in Sleep Regulation

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Krueger, James·2008·Current Pharmaceutical Design

DOI 10.2174/138161208786549281PMC PMC2692603

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Abstract

Interleukin-1 beta (IL1) and tumor necrosis factor alpha (TNF) promote non-rapid eye movement sleep under physiological and inflammatory conditions. Additional cytokines are also likely involved but evidence is insufficient to conclude that they are sleep regulatory substances. Many of the symptoms induced by sleep loss, e.g. sleepiness, fatigue, poor cognition, enhanced sensitivity to pain, can be elicited by injection of exogenous IL1 or TNF. We propose that ATP, released during neurotransmission, acting via purine P2 receptors on glia releases IL1 and TNF. This mechanism may provide the means by which the brain keeps track of prior usage history. IL1 and TNF in turn act on neurons to change their intrinsic properties and thereby change input-output properties (i.e. state shift) of the local network involved. Direct evidence indicates that cortical columns oscillate between states, one of which shares properties with organism sleep. We conclude that sleep is a local use-dependent process influenced by cytokines and their effector molecules such as nitric oxide, prostaglandins and adenosine.

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Authors: Krueger, J.
Affiliations: Washington State University (US)
Corresponding author: Krueger, James
Venue: Current Pharmaceutical Design
Publisher: Bentham Science Publishers Ltd.
Published: 2008-11-01
Volume: 14
Issue: 32
Pages: 3408-3416
ISSN: 1381-6128 (ISSN-L)
DOI: 10.2174/138161208786549281
PMC: PMC2692603
OpenAlex: W2023517019
Cited by: 507
References: 114
Citations by year: 2026: 18 · 2025: 42 · 2024: 43 · 2023: 32 · 2022: 28 · 2021: 32 · 2020: 30 · 2019: 33 · 2018: 19 · 2017: 23 · 2016: 27 · 2015: 19 · 2014: 31 · 2013: 52 · 2012: 26
FWCI: 8.96
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Current Pharmaceutical Design (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Neurological Disorders and Stroke (NS-31453, NS-25378, R01NS031453, R01NS027250, R01NS025378)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-36520, R01HD036520)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Keywords: cytokines, sleep regulation, IL-1β, TNF-α, NREM sleep, ATP release, purinergic P2 receptors, glial activation, sleep deprivation, cortical columns, cortical oscillations, nitric oxide, prostaglandins, adenosine
MeSH terms: Humans, Sleep, Cytokines

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