The DOI matches its Crossref record; 49 of the 55 references it cites were found in a registry or an index.
Involvement of cytokines in slow wave sleep
Open accessAbstract
Cytokines such as tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL1β) play a role in sleep regulation in health and disease. TNFα or IL1β injection enhances non-rapid eye movement sleep. Inhibition of TNFα or IL1β reduces spontaneous sleep. Mice lacking TNFα or IL1β receptors sleep less. In normal humans and in multiple disease states, plasma levels of TNFα covary with EEG slow wave activity (SWA) and sleep propensity. Many of the symptoms induced by sleep loss, for example, sleepiness, fatigue, poor cognition, enhanced sensitivity to pain, are elicited by injection of exogenous TNFα or IL1β. IL1β or TNFα applied unilaterally to the surface of the cortex induces state-dependent enhancement of EEG SWA ipsilaterally, suggesting greater regional sleep intensity. Interventions such as unilateral somatosensory stimulation enhance localized sleep EEG SWA, blood flow, and somatosensory cortical expression of IL1β and TNFα. State oscillations occur within cortical columns. One such state shares properties with whole animal sleep in that it is dependent on prior cellular activity, shows homeostasis, and is induced by TNFα. Extracellular ATP released during neuro- and gliotransmission enhances cytokine release via purine type 2 receptors. An ATP agonist enhances sleep, while ATP antagonists inhibit sleep. Mice lacking the P2X7 receptor have attenuated sleep rebound responses after sleep loss. TNFα and IL1β alter neuron sensitivity by changing neuromodulator/neurotransmitter receptor expression, allowing the neuron to scale its activity to the presynaptic neurons. TNFα's role in synaptic scaling is well characterized. Because the sensitivity of the postsynaptic neuron is changed, the same input will result in a different network output signal and this is a state change. The top-down paradigm of sleep regulation requires intentional action from sleep/wake regulatory brain circuits to initiate whole-organism sleep. This raises unresolved questions as to how such purposeful action might itself be initiated. In the new paradigm, sleep is initiated within networks and local sleep is a direct consequence of prior local cell activity. Whole-organism sleep is a bottom-up, self-organizing, and emergent property of the collective states of networks throughout the brain.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The neurobiological mechanisms underlying the hourglass are not characterized as well as the mechanisms of the clock are. As reviewed elsewhere in the present special issue and several times before, important roles have been assigned to adenosine [66], to an increase in synaptic density during wakefulness [79], and to cytokines [50].”
From Sleep, vigilance, and thermosensitivity (2012) · cites this paper as [50]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Two-Process Model of Sleep Regulation
Binder, M. D., Hirokawa, N., & Windhorst, U. (2008) · Springer eBooks · doi:10.1007/978-3-540-29678-2_6166 · Cited by 3,900
Hypothalamic regulation of sleep and circadian rhythms
Saper, C. B., Scammell, T. E., & Lu, J. (2005) · Nature · doi:10.1038/nature04284 · Cited by 2,804
Synaptic scaling mediated by glial TNF-α
Stellwagen, D., & Malenka, R. C. (2006) · Nature · doi:10.1038/nature04671 · Cited by 1,715
The self-tuning neuron: synaptic scaling of excitatory synapses
Turrigiano, G. G. (2008) · Cell · doi:10.1016/j.cell.2008.10.008 · Cited by 1,533
Sleep and synaptic homeostasis: a hypothesis
Tononi, G., & Cirelli, C. (2003) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2003.09.004 · Cited by 1,217
The P2X7 Receptor: A Key Player in IL-1 Processing and Release
Ferrari, D., Pizzirani, C., Adinolfi, E., Lemoli, R. M., Curti, A., Idzko, M., Panther, E., & Di Virgilio, F. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.7.3877 · Cited by 1,025
Vgontzas, A. N., Papanicolaou, D. A., Bixler, E. O., Kales, A., Tyson, K., & Chrousos, G. P. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.5.3950 · Cited by 974
Cortical firing and sleep homeostasis
Vyazovskiy, V. V., Olcese, U., Lazimy, Y. M., Faraguna, U., Esser, S. K., Williams, J. C., Cirelli, C., & Tononi, G. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.024 · Cited by 740
Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation.
Tracey, K. J., He, W., Manogue, K. R., Fong, Y., HESSE, D. G., Nguyen, H. T., Kuo, G. C., Beutler, B., Cotran, R. S., & Cerami, A. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.3.1211 · Cited by 730
Lähdevirta, J., Maury, C. P. J., Teppo, A., & Repo, H. (1988) · The American Journal of Medicine · doi:10.1016/0002-9343(88)90576-1 · Cited by 717
How (and why) the immune system makes us sleep
Imeri, L., & Opp, M. R. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2576 · Cited by 710
Sleep as a fundamental property of neuronal assemblies
Krueger, J. M., Rector, D. M., Roy, S., Van Dongen, H. P. A., Belenky, G., & Panksepp, J. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2521 · Cited by 596
Self-citationThe Role of Cytokines in Sleep Regulation
Krueger, J. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208786549281 · Cited by 507
Self-citationSleep-promoting effects of endogenous pyrogen (interleukin-1)
Krueger, J. M., Walter, J., Dinarello, C. A., Wolff, S. M., & CHEDID, L. A. (1984) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1984.246.6.r994 · Cited by 456
Self-citationOpp, M. R. (2005) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2005.01.002 · Cited by 393
Vince, G. S., Starkey, P. M., Austgulen, R., Kwiatkowski, D., & Redman, C. W. G. (1995) · BJOG: An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1995.tb09020.x · Cited by 381
Vgontzas, A. N., Zoumakis, E., Lin, H. ‐., Bixler, E. O., Trakada, G., & Chrousos, G. P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031929 · Cited by 345
Biochemical regulation of non-rapid-eye-movement sleep
Krueger, J. M. (2003) · Frontiers in Bioscience · doi:10.2741/1033 · Cited by 329
Self-citationA neuronal group theory of sleep function
Krueger, J. M., & Obál, F. (1993) · Journal of Sleep Research · doi:10.1111/j.1365-2869.1993.tb00064.x · Cited by 315
Self-citationRecombinant tumor necrosis factor and interleukin 1 enhance slow-wave sleep
Shoham, S., Davenne, D., Cady, A. B., Dinarello, C. A., & Krueger, J. M. (1987) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1987.253.1.r142 · Cited by 290
Self-citationLinks between the innate immune system and sleep
Majde, J. A., & Krueger, J. M. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.08.005 · Cited by 277
Self-citationPappenheimer, J. R., Koski, G., Fencl, V., Karnovsky, M. L., & Krueger, J. M. (1975) · Journal of Neurophysiology · doi:10.1152/jn.1975.38.6.1299 · Cited by 270
Self-citationObstructive Sleep Apnea Syndrome and Circadian Rhythms of Hormones and Cytokines
Entzian, P., Linnemann, K., Schlaak, M. S., & Zabel, P. (1996) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.153.3.8630548 · Cited by 248
Cellular and molecular connections between sleep and synaptic plasticity
Benington, J. H., & Frank, M. G. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(03)00018-2 · Cited by 244
Circulating tumour necrosis factor‐α (cachectin) in myocardial infarction
Maury, C. P. J., & Teppo, A. M. (1989) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.1989.tb00090.x · Cited by 174
Mice Lacking the TNF 55 kDa Receptor Fail to Sleep More After TNFα Treatment
Fang, J., Wang, Y., & Krueger, J. M. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-15-05949.1997 · Cited by 167
Self-citationAlteration of sleep in rabbits by Staphylococcus aureus infection
Toth, L. A., & Krueger, J. M. (1988) · Infection and Immunity · doi:10.1128/iai.56.7.1785-1791.1988 · Cited by 159
Self-citationLocal functional state differences between rat cortical columns
Rector, D. M., Topchiy, I., Carter, K. M., & Rojas, M. J. (2005) · Brain Research · doi:10.1016/j.brainres.2005.04.002 · Cited by 159
Effects of interleukin-1β on sleep are mediated by the type I receptor
Fang, J., Wang, Y., & Krueger, J. M. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.3.r655 · Cited by 152
Self-citationKapsimalis, F., Richardson, G. S., Opp, M. R., & Kryger, M. H. (2005) · Current Opinion in Pulmonary Medicine · doi:10.1097/01.mcp.0000183062.98665.6b · Cited by 150
Krueger, J. M., Rector, D. M., & Churchill, L. (2007) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2007.03.003 · Cited by 128
Self-citationBurnstock, G. (2008) · Experimental Physiology · doi:10.1113/expphysiol.2008.043620 · Cited by 128
Sleep and Cerebrospinal Fluid Interleukin-1-Like Activity in the Cat
Lue, F. A., Bail, M., Jephthah-Ochola, J., Carayanniotis, K., Gorczynski, R. M., & Moldofsky, H. (1988) · International Journal of Neuroscience · doi:10.3109/00207458808991595 · Cited by 116
Tumor necrosis factor and HIV P24 antigen levels in serum of HIV-infected populations.
Reddy, M. M., Sorrell, S., Lange, M., & Grieco, M. H. (1988) · PubMed · Cited by 109
Alam, M. N., McGinty, D., Bashir, T., Kumar, S., Imeri, L., Opp, M. R., & Szymusiak, R. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03469.x · Cited by 108
Calcium signaling in specialized glial cells
Metea, M. R., & Newman, E. A. (2006) · Glia · doi:10.1002/glia.20352 · Cited by 97
Intrapreoptic microinjection of TNF-α enhances non-REM sleep in rats
Kubota, T., Li, N., Guan, Z., Brown, R. A., & Krueger, J. M. (2002) · Brain Research · doi:10.1016/s0006-8993(02)02262-x · Cited by 92
Self-citationATP and the purine type 2 X7 receptor affect sleep
Krueger, J. M., Taishi, P., De, A., Davis, C. J., Winters, B. D., Clinton, J. M., Szentirmai, É., & Zielinski, M. R. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00586.2010 · Cited by 88
Self-citationSpontaneous and influenza virus-induced sleep are altered in TNF-α double-receptor deficient mice
Kapás, L., Bohnet, S. G., Traynor, T. R., Majde, J. A., Szentirmai, É., Magrath, P., Taishi, P., & Krueger, J. M. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.90388.2008 · Cited by 75
Self-citationThe effect of interleukin-1 blockade on fatigue in rheumatoid arthritis—a pilot study
Omdal, R., & Gunnarsson, R. (2004) · Rheumatology International · doi:10.1007/s00296-004-0463-z · Cited by 71
Sleep and dynamic stabilization of neural circuitry: A review and synthesis
Kavanau, J. L. (1994) · Behavioural Brain Research · doi:10.1016/0166-4328(94)90082-5 · Cited by 67
Enhancement of slow-wave sleep by tumor necrosis factor-α is mediated by cyclooxygenase-2 in rats
Terao, A., Matsumura, H., Yoneda, H., & Saito, M. (1998) · NeuroReport · doi:10.1097/00001756-199812010-00005 · Cited by 60
Imeri, L., Opp, M. R., & Krueger, J. M. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.265.4.r907 · Cited by 59
Self-citationA network model for activity-dependent sleep regulation
Roy, S., Krueger, J. M., Rector, D. M., & Wan, Y. (2008) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2008.03.033 · Cited by 56
Self-citationTakahashi, S., Kapás, L., & Krueger, J. M. (1996) · Journal of Sleep Research · doi:10.1046/j.1365-2869.1996.d01-63.x · Cited by 54
Self-citationHallett, H., Churchill, L., Taishi, P., De, A., & Krueger, J. M. (2010) · Brain Research · doi:10.1016/j.brainres.2010.03.048 · Cited by 49
Self-citationClinical experience with soluble TNF p75 receptor in rheumatoid arthritis
Franklin, C. M. (1999) · Seminars in Arthritis and Rheumatism · doi:10.1016/s0049-0172(99)80028-6 · Cited by 49
(1996) · International Journal of Gynecology & Obstetrics · doi:10.1016/0020-7292(96)82802-5 · Cited by 49
Postdialysis fatigue: Lack of effect of a biocompatible membrane
Sklar, A. H., Beezhold, D. H., Newman, N., Hendrickson, T., & DREISBACH, A. (1998) · American Journal of Kidney Diseases · doi:10.1053/ajkd.1998.v31.pm9631846 · Cited by 43
Cited by
Sorted by citations
Neural Circuitry of Wakefulness and Sleep
Scammell, T. E., Arrigoni, E., & Lipton, J. O. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.014 · Cited by 966
Möller-Levet, C. S., Archer, S. N., Bucca, G., Laing, E. E., Slak, A., Kabiljo, R., Lo, J. C. Y., Santhi, N., von Schantz, M., Smith, C. P., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217154110 · Cited by 576
Functions and Mechanisms of Sleep
Zielinski, M. R., McKenna, J. T., & McCarley, R. W. (2016) · AIMS neuroscience · doi:10.3934/neuroscience.2016.1.67 · Cited by 392
Self-citationNeural circuitry engaged by prostaglandins during the sickness syndrome
Saper, C. B., Romanovsky, A. A., & Scammell, T. E. (2012) · Nature Neuroscience · doi:10.1038/nn.3159 · Cited by 285
Crosstalk between the circadian clock circuitry and the immune system
Cermakian, N., Lange, T., Golombek, D., Sarkar, D., Nakao, A., Shibata, S., & Mazzoccoli, G. (2013) · Chronobiology International · doi:10.3109/07420528.2013.782315 · Cited by 279
Metadata
- Authors
- Krueger, J. M., Clinton, J. M., Winters, B. D., Zielinski, M. R., Taishi, P., Jewett, K. A., & Davis, C. J.
- Affiliations
- Washington State University Spokane (US)
- Corresponding author
- Krueger, James M.
- Venue
- Progress in Brain Research
- Publisher
- Elsevier
- Published
- 2011
- Volume
- 193
- Pages
- 39-47
- ISSN
- 0079-6123 (ISSN-L)
- PMC
- PMC3645329
- OpenAlex
- W3779999
- Cited by
- 126
- References
- 55
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 3 · 2023: 7 · 2022: 9 · 2021: 13 · 2020: 4 · 2019: 10 · 2018: 11 · 2017: 9 · 2016: 3 · 2015: 11 · 2014: 6 · 2013: 17 · 2012: 6
- FWCI
- 21.11
- Type
- book chapter
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Progress in brain research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- W. M. Keck Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS-31453, NS-25378, R01NS031453, 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
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- cytokines, slow-wave sleep, TNF-α, IL-1β, sleep regulation, EEG slow-wave activity, sleep deprivation, P2X7 receptor, extracellular ATP, synaptic scaling, somatosensory cortex, sleep homeostasis, sleep initiation, neuroinflammation
- MeSH terms
- Animals, Brain, Humans, Sleep, Tumor Necrosis Factor-alpha, Signal Transduction, Cytokines, Interleukin-1beta, Receptors, Purinergic P2Y1, Receptors, Purinergic P2X7
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 ›
Are you an author, or do you see a problem with this page? Request a review
