Interleukin 1 alters rat sleep: temporal and dose-related effects
Abstract
Rats received various doses of interleukin 1 (IL-1) (range, 0.5-25.0 ng) or pyrogen-free saline intracerebroventricularly during the rest (light) and the active (dark) cycles of the day, and sleep-wake activity and brain temperature were determined for 6 h. Low doses of IL-1 (0.5 ng at night, 2.5 ng during the day) increased both the duration of non-rapid-eye-movement sleep (NREMS) and electroencephalogram (EEG) slow-wave activity during NREMS episodes. Increasing doses of IL-1 had divergent effects on NREMS duration and EEG slow-wave activity, and the direction of the changes depended on the diurnal cycle. Thus NREMS duration was promoted at night and EEG slow-wave amplitudes during the day, whereas NREMS duration during the day and EEG slow-wave amplitudes at night were suppressed after higher doses of IL-1. High doses of IL-1 also induced decreases in rapid-eye-movement sleep during both phases of the day. Each dose of IL-1 that promoted NREMS also tended to increase brain temperature. These results demonstrate that IL-1 promotes NREMS in the rat. However, unlike previously reported findings in rabbits, the circadian rhythm of sleep regulation strongly interferes with the sleep-promoting activity of IL-1 in rats.
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IL-1 and TNF are substances involved in the homeostatic regulation of sleep.
“These findings established both cytokines, IL-1 and TNF, as substances involved in the homeostatic regulation of sleep (for review, see Refs. 299, 411).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [411]
Increasing the availability of IL-1 and TNF promotes NREM sleep amount and intensity and suppresses REM sleep amount.
“increasing the availability of those cytokines promoted NREM sleep amount and intensity and suppressed REM sleep amount.”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [411]
Blocking the biological actions of IL-1 and TNF reduces physiological NREM sleep amount or NREM sleep rebound after sleep deprivation.
“blocking the biological actions of the cytokines IL-1 and TNF resulted in a reduction of physiological NREM sleep amount or NREM sleep rebound after sleep deprivation.”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [411]
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Epidermal growth factor enhances spontaneous sleep in rabbits
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“For example, intraperitoneal injections of IL-1b or TNF induce increases in NREMS and decreases in EEG SWA in rats (10) and mice (8), whereas intracerebroventricular injections of IL-1 or TNF enhance both (11, 27).”
Self-citationOpp, M. R., Postlethwaite, A. E., Seyer, J. M., & Krueger, J. M. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.9.3726 · Cited by 55 · see citing works
Self-citationRole of Cytokines in Infection‐Induced Stressa
Dunn, A. J. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb49932.x · Cited by 55 · see citing works
Cafeteria diet-induced sleep is blocked by subdiaphragmatic vagotomy in rats
Hansen, M. K., Kapás, L., Fang, J., & Krueger, J. M. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.1.r168 · Cited by 54 · see citing works
“In rats, during the day low doses of IL-1b increase EEG SWA and NREMS, whereas during the night the same dose of IL-1b decreases EEG SWAbut still increases NREMS (26).”
BackgroundSelf-citationRole of corticotropin-releasing hormone in stressor-induced alterations of sleep in rat
Chang, F., & Opp, M. R. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00758.2001 · Cited by 54 · see citing works
“In addition, we (28, 29, 36) have previously shown that the impact of immune challenge on sleep-wake behavior depends on the time of day at which the challenge occurs.”
BackgroundSelf-citationOlivadoti, M. D., & Opp, M. R. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.02.008 · Cited by 53 · see citing works
Self-citationBeranek, L., Hajdu, I., Gardi, J., Taishi, P., Obál, F., & Krueger, J. M. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.5.r1297 · Cited by 52 · see citing works
“The magnitude of the increments in delta power during NREMS after Oct is comparable to the SWA response to sleeppromoting doses of interleukin-1 during the light cycle in the rat (33) or to the increases in delta power elicited by preoptic heating in the cat (25).”
MethodSelf-citationBaker, F. C., Shah, S., Stewart, D., Angara, C., Gong, H., Szymusiak, R. S., Opp, M. R., & McGinty, D. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00615.2004 · Cited by 51 · see citing works
“When administered into rats at dark onset, effective doses of IL-1 induce biphasic effects on NREM sleep; there is an initial increase in NREM sleep during the first hour, and a more prominent increase 4–5 h postinjection (26, 29).”
BackgroundMethodInfluentialSelf-citationInfluence of host defense activation on sleep in humans
Pollmächer, T., Mullington, J. M., Korth, C., & Hinze‐Selch, D. (1995) · Advances in Neuroimmunology · doi:10.1016/0960-5428(95)00006-n · Cited by 48 · see citing works
Sleep and Psychoneuroimmunology
Opp, M. R. (2009) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2009.02.009 · Cited by 47 · see citing works
Self-citationImeri, L., Mancia, M., & Opp, M. R. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00006-8 · Cited by 47 · see citing works
Self-citationCentral nervous system and peripheral immune functions and the sleep-wake system.
Moldofsky, H. (1994) · PubMed Central · Cited by 47 · see citing works
Food Restriction Alters the Diurnal Distribution of Sleep in Rats
Roky, R., Kapás, L., Taishi, P., Fang, J., & Krueger, J. M. (1999) · Physiology & Behavior · doi:10.1016/s0031-9384(99)00137-7 · Cited by 45 · see citing works
“Thus, the effects of interelukin-1 on these parameters are independent, and differentially depend on the time of day interleukin-1 is given; for example, high doses of interleukin-1 given intracerebroventricularly to rats inhibit NREMS yet enhance EEG SWA (low doses enhance both) (33).”
BackgroundSelf-citationThe effect of restraint stress on paradoxical sleep is influenced by the circadian cycle
Koehl, M., Bouyer, J. J., Darnaudéry, M., Moal, M. L., & Mayo, W. (2002) · Brain Research · doi:10.1016/s0006-8993(02)02463-0 · Cited by 45 · see citing works
Modulation of Neural Networks by Interleukin-1
Nemeth, D. P., & Quan, N. (2020) · Brain Plasticity · doi:10.3233/bpl-200109 · Cited by 44 · see citing works
“For example, IL-1 levels were found to vacillate with circadian rhythm [15] and influence normal sleep [16, 17].”
BackgroundBabiloni, A. H., Baril, A., Charlebois‐Plante, C., Jodoin, M., Sanchez, E., Baets, L. D., Arbour, C., Lavigne, G. J., Gosselin, N., & Beaumont, L. D. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12051793 · Cited by 43 · see citing works
“However, some of these effects seem to be level dependent, where an inverse relation can be observed at higher levels, with high pro-inflammatory cytokines levels being associated with disrupted and fragmented sleep [75].”
BackgroundSleep inflammation and cardiovascular disease
Meier-Ewert, H. K. (2012) · Frontiers in Bioscience-Elite · doi:10.2741/e560 · Cited by 43 · see citing works
- Authors
- Opp, M. R., Obal, F., & Krueger, J. M.
- Affiliations
- University of Tennessee Health Science Center (US)
- Department of Physiology and Biophysics, University of Tennessee,Memphis 38163.
- ORCID
- Opp, M. R.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 1991-01-01
- Volume
- 260
- Issue
- 1
- Pages
- R52-R58
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2286922506
- Cited by
- 232
- References
- 0
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 6 · 2018: 1 · 2017: 6 · 2016: 5 · 2015: 6 · 2014: 3 · 2013: 7 · 2012: 7
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-27250, NS-25378, R01NS027250, R01NS025378)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- interleukin-1, sleep regulation, NREM sleep, REM sleep, EEG slow-wave activity, circadian rhythm, dose-dependent effects, brain temperature, intracerebroventricular administration, rats
- MeSH terms
- Animals, Brain, Circadian Rhythm, Dose-Response Relationship, Drug, Electroencephalography, Interleukin-1, Light, Male, Rats, Inbred Strains, Sleep, REM, Temperature, Rats
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