Interleukin-18 promotes sleep in rabbits and rats
Abstract
Interleukin (IL)-1β is involved in physiological sleep regulation. IL-18 is a member of the IL-1 family, and its signal-transduction mechanism is similar to that of IL-1. Therefore, we hypothesized that IL-18 might also be involved in sleep regulation. Three doses of IL-18 (10, 100, and 500 ng) were injected intracerebroventricularly (icv) into rabbits at the onset of the dark period. The two higher doses of IL-18 markedly increased non-rapid eye movement sleep (NREMS), accompanied by increases in brain temperature (Tbr). These effects were lost after the heat inactivation of IL-18. The 500 ng of IL-18 injection during the light period also increased NREMS and Tbr. Similar results were obtained after icv injection of 100 ng of IL-18 into rats. Furthermore, intraperitoneal injection of 30 μg/kg of IL-18 slightly, but significantly, increased NREMS, whereas it significantly decreased electroencephalogram slow-wave activity in rats. Intraperitoneal IL-18 failed to induce fever. An anti-human IL-18 antibody had little effect on spontaneous sleep in rabbits, although the anti-IL-18 antibody significantly attenuated muramyl dipeptide-induced sleep. These data suggest that IL-18 is involved in mechanisms of sleep responses to infection.
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IL-1beta, TNFalpha, and IL-18 are inducers of nonrapid eye movement sleep.
“IL-1b,21 TNFa22, and IL-1823 are inducers of nonrapid eye movement (nREM) sleep.”
From The Gut Microbiome and the Brain (2014) · cites this paper as [23]
The anti-inflammatory cytokines IL-4, IL-10, and IL-13 attenuate NREM sleep amount in rabbits.
“The anti-inflammatory cytokines IL-4, IL-10, and IL-13 have been reported to attenuate NREM sleep amount in rabbits (308, 314, 315)”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [308]
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- Authors
- Kubota, T., Fang, J., Brown, R. A., & Krueger, J. M.
- Affiliations
- Washington State University (US)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2001-09-01
- Volume
- 281
- Issue
- 3
- Pages
- R828-R838
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2182574817
- Cited by
- 69
- References
- 60
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 2 · 2017: 2 · 2016: 1 · 2014: 4 · 2013: 2 · 2012: 1
- FWCI
- 3.27
- 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-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 › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- IL-18, sleep regulation, NREM sleep, interleukin-1 family, intracerebroventricular administration, brain temperature, fever, slow-wave activity, muramyl dipeptide, rabbits, rats
- MeSH terms
- Acetylmuramyl-Alanyl-Isoglutamine, Animals, Antibodies, Body Temperature, Brain, Darkness, Dose-Response Relationship, Drug, Electroencephalography, Fever, Injections, Intraperitoneal, Injections, Intraventricular, Light, Male, Rabbits, Sleep, Sleep Stages, Specific Pathogen-Free Organisms, Signal Transduction, Rats, Sprague-Dawley, Photoperiod, Interleukin-18, Rats
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