Cited by 158Sleep and Wakefulness ResearchSleep and Work-Related FatigueTryptophan and brain disorders

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REM Sleep Deprivation in Rats Results in Inflammation and Interleukin-17 Elevation

Yehuda, Shlomo, Sredni, Benjamin, Carasso, Rafi L., Kenigsbuch-Sredni, Dvora·2009·Journal of Interferon & Cytokine Research

DOI 10.1089/jir.2008.0080

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Abstract

Sleep deprivation is a major health problem in modern society. Deprivation of rapid eye movement (REM) sleep is particularly damaging to cognition and to spatial memory; however, the mechanisms that mediate these deteriorations in function are not known. We explored the possibility that REM sleep deprivation may provoke major changes in the immune system by inducing inflammation. Rats were subjected to 72 h of REM sleep deprivation, and the plasma levels of proinflammatory cytokines (IL-1, IL-1beta, IL-6, IL-17A, and TNF-alpha), an anti-inflammatory cytokine (IL-10), the inflammatory markers homocysteine, corticosterone, and hyperthermia were measured immediately after the deprivation period, and 7 days later. The results indicate that REM sleep deprivation induced an inflammatory response. The levels of the proinflammatory cytokines and markers were significantly elevated in sleep-deprived rats as compared to control rats. After 7 days of recovery, the levels of some markers, including hyperthermia, remained higher in sleep-deprived rats versus the control animals. IL-17A appears to play a pivotal role in coordinating the inflammation. These data shed new light on the mechanism of sleep deprivation-induced inflammation.

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Sleep Deprivation Induces Changes in Immunity in Trichinella spiralis -Infected Rats
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“IL-10, ΤΝF−α and IL-17 [17].”
Sleep deprivation of rats increases postsurgical expression and activity of L-type calcium channel in the dorsal root ganglion and slows recovery from postsurgical pain
Li, Q., Zhu, Z.-Y., Lu, J., Chao, Y.-C., Zhou, X., Huang, Y., Chen, X., Su, D., Yu, W., & Gu, X. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0868-2 · Cited by 29
Association between sleep disorders and subsequent chronic spontaneous urticaria development
He, G.-Y., Tsai, T., Lin, C.-L., Shih, H.-M., & Hsu, T.-Y. (2018) · Medicine · doi:10.1097/md.0000000000011992 · Cited by 123
Bidirectional association between alopecia areata and sleep disorders: a population-based cohort study in Taiwan
Dai, Y., Tai, Y., Chen, C., Chang, Y.-T., Chen, T., & Chen, M. (2020) · Sleep Medicine · doi:10.1016/j.sleep.2020.06.015 · Cited by 27
Sleep disturbances and the risk of lung cancer: a meta-epidemiological study
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“This is due to the activation of proinflammatory cytokine secretion, which induces an inflammatory microenvironment in both animal models and humans [31, 32].”
Background
Biochemical modulation of the sleep–wake cycle: Endogenous sleep‐inducing factors
Arias-Carrión, Ó., Huitrón‐Reséndiz, S., Arankowsky‐Sandoval, G., & Murillo‐Rodríguez, E. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22666 · Cited by 26
“Furthermore, brain levels of IL-1b and TNFa correlate with sleep propensity, insofar as it has been observed that levels of these molecules are enhanced after sleep deprivation (Yehuda et al., 2009).”
Background
REM sleep loss–induced elevated noradrenaline could predispose an individual to psychosomatic disorders: a review focused on proposal for prediction, prevention, and personalized treatment
Mehta, R., Giri, S., & Mallick, B. N. (2020) · The EPMA Journal · doi:10.1007/s13167-020-00222-1 · Cited by 24
The biological clock enhancer nobiletin ameliorates steatosis in genetically obese mice by restoring aberrant hepatic circadian rhythm
Larion, S., Padgett, C. A., Butcher, J. T., MINTZ, J. D., Fulton, D. J., & Stepp, D. W. (2022) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00130.2022 · Cited by 25
Protective effects of a probiotic-fermented germinated grain complex on neurotransmitters and sleep quality in sleep-deprived mice
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The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions
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“In addition, sleep fragmentation enhances plasma inflammatory cytokines (e.g., TNF-α, IL-6, IL-1α, and IL-1β), leading to increased oxidative stress and inflammation (Yehuda et al., 2009).”
Background
The inhibitory effect of sleep deprivation on cell proliferation in the hippocampus of adult mice is eliminated by corticosterone clamp combined with interleukin-1 receptor 1 knockout
Mueller, A. D., Parfyonov, M., Pavlovski, I., Marchant, E. G., & Mistlberger, R. E. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.10.001 · Cited by 23
“…is evidence that pro-inflammatory cytokines are activated by sleep deprivation (Hu et al., 2003; Everson, 2005; Krueger, 2008; Imeri and Opp, 2009; Yehuda et al., 2009), and that IL-1b mediates behavioral and antineurogenic effects of different types of acute and chronic stress in rodents (Goshen…”
Stress systems exacerbate the inflammatory response after corneal abrasion in sleep-deprived mice via the IL-17 signaling pathway
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Inflammatory markers are associated with inhibitory avoidance memory deficit induced by sleep deprivation in rats
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“the immune system that can persist after recovery sleep (Yehuda et al., 2009) suggesting a possible role for REM in the neuroimmune responses induced by stress.”
Background
The multifaceted impact of circadian disruption on cancer risk: a systematic review of insights and economic implications
Clemente‐Suárez, V. J., Navarro-Jiménez, E., Benítez-Agudelo, J. C., Beltrán-Velasco, A. I., Belinchón-deMiguel, P., Ramos‐Campo, D. J., Villanueva-Tobaldo, C. V., Martín-Rodríguez, A., & Tornero-Aguilera, J. F. (2025) · Journal of the National Cancer Center · doi:10.1016/j.jncc.2025.04.005 · Cited by 25
“88 Animal research supports this, with rats deprived of REM sleep exhibiting persistently high levels of proinﬂammatory markers (e.g., IL-6, TNF-𝛼 , IL-17, IL-1 𝛽 , corticosterone, homocysteine), even after recovery sleep.”
Association of Sleep Deprivation and the Risk of Developing Systemic Lupus Erythematosus Among Women
Choi, M. Y., Malspeis, S., Sparks, J. A., Cui, J., Yoshida, K., & Costenbader, K. H. (2022) · Arthritis Care & Research · doi:10.1002/acr.25017 · Cited by 23
“markers of inflammation such as corticosterone have been reported, while antiinflammatory cytokine IL-10 did not change (17).”
Background
Differential effects of total and partial sleep deprivation on salivary factors in Wistar rats
Lasisi, T. J., Shittu, S.-T. T., Meludu, C., & Salami, A. A. (2016) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2016.09.002 · Cited by 19
Cytokine and microRNA levels during different periods of paradoxical sleep deprivation and sleep recovery in rats
Brianza-Padilla, M., Sánchez‐Muñoz, F., Vázquez-Palacios, G., Huang, F., Almanza-Pérez, J. C., Bojalil, R., & Bonilla‐Jaime, H. (2018) · PeerJ · doi:10.7717/peerj.5567 · Cited by 19
Short-Term Sleep Loss Alters Cytokine Gene Expression in Brain and Peripheral Tissues and Increases Plasma Corticosterone of Zebra Finch ( Taeniopygia guttata )
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Social sleepers: The effects of social status on sleep in terrestrial mammals
Smeltzer, E. A., Stead, S. M., Li, M. F., Samson, D. R., Kumpan, L. T., & Teichroeb, J. A. (2022) · Hormones and Behavior · doi:10.1016/j.yhbeh.2022.105181 · Cited by 19
The Role of Essential Fatty Acids in Anorexia Nervosa and Obesity
Yehuda, S., & Rabinovitz, S. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2013.809690 · Cited by 17
“Pretreatment with a mixture of omega-3 and omega-6 fatty acids rehabilitated the behavioral and immunological effects of sleep deprivation (Yehuda et al., 2007, 2009).”
BackgroundSelf-citation
Chronic noise exposure in the spontaneously hypertensive rat
Michaud, D. S., Konkle, A. T. M., Keith, S. E., & McNamee, J. P. (2017) · Noise and Health · doi:10.4103/nah.nah_15_17 · Cited by 17
“Some studies, but not all([47]) have found that sleep disruption in rats leads to an increase in circulating([48,49]) and cerebral([50]) levels and expression, respectively, of IL-6, IL-1 and TNF-alpha.”
Background
Sleep and Alzheimer: The Link
Archana Gaur, T., Kaliappan, A., Balan, Y., Sakthivadivel, V., Medala, K., & Umesh, M. (2022) · MAEDICA – a Journal of Clinical Medicine · doi:10.26574/maedica.2022.17.1.177 · Cited by 19
Innate immunity modulation in the duodenal mucosa induced by REM sleep deprivation during infection with Trichinella spirallis
Ibarra‐Coronado, E., Pérez‐Torres, A., Pantaleón-Martínez, A. M., Velázquez‐Moctezuma, J., Rodríguez‐Mata, V., & Morales‐Montor, J. (2017) · Scientific Reports · doi:10.1038/srep45528 · Cited by 15
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Sleep Deprivation Interferes with JAK/STAT Signaling Pathway and Myogenesis in the Masseter Muscle of Rats
Galvani, M. G., Antunes, H. K. M., Mônico‐Neto, M., Yujra, V. Q., Prado, C. M., Quintana, H. T., de Oliveira, F., & Ribeiro, D. A. (2021) · Medical Principles and Practice · doi:10.1159/000515307 · Cited by 13
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Background
The impact on the quality of life and sleep complaints in a vitiligo sample and the influence of inflammatory cytokines in the interaction between vitiligo and sleep
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“Of note, recent studies have suggested that interactions between BDNF and inflammation exist,(9) whereas research in both humans and rodents supports the detrimental effect of sleep loss on the peripheral inflammatory status.(3,4) In the present study, we found that serum TNF-α and IL-6 levels were significantly highe…”
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Effect of Sleep Loss on Pain
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Authors: Yehuda, S., Sredni, B., Carasso, R. L., & Kenigsbuch-Sredni, D.
Affiliations: Bar-Ilan University (IL)
Hillel Yaffe Medical Center (IL)
Interdisciplinary Department, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
ORCID: Sredni, Benjamin
Venue: Journal of Interferon & Cytokine Research
Publisher: SAGE Publications
Published: 2009-07
Volume: 29
Issue: 7
Pages: 393-398
ISSN: 1079-9907 (ISSN-L)
1557-7465
DOI: 10.1089/jir.2008.0080
OpenAlex: W2024940102
Semantic Scholar: 0c21c44497e54bddb2003dcb6e50f30e93f94345
Cited by: 158
References: 47
Citations by year: 2026: 7 · 2025: 5 · 2024: 11 · 2023: 12 · 2022: 22 · 2021: 8 · 2020: 10 · 2019: 12 · 2018: 6 · 2017: 13 · 2016: 8 · 2015: 7 · 2014: 6 · 2013: 12 · 2012: 6
FWCI: 3.06
Type: journal article
Language: en
Open access: closed
Licence: www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations: Journal of Interferon & Cytokine Research (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: REM sleep deprivation, sleep deprivation, inflammation, IL-17A, inflammatory cytokines, IL-1β, interleukin-6, TNF-α, IL-10, homocysteine, corticosterone, hyperthermia, immune system, sleep and immunity
MeSH terms: Animals, Corticosterone, Fever, Homocysteine, Inflammation, Male, Sleep Deprivation, Biomarkers, Up-Regulation, Rats, Long-Evans, Interleukin-17, Rats

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REM Sleep Deprivation in Rats Results in Inflammation and Interleukin-17 Elevation

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