The roles of prostaglandin E2 and D2 in lipopolysaccharide-mediated changes in sleep
Open accessAbstract
When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE2 is the principal mediator of fever, and both PGE2 and PGD2 regulate sleep-wake behavior. The extent to which PGE2 and PGD2 are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE2 receptors type EP3 or EP4, in mice with total body KO of microsomal PGE synthase-1 or the PGD2 receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP4 receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP3 receptors or in the presence of a COX inhibitor.
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Chronic sleep disturbances may be the cause or the consequence of other known triggers of low-grade inflammation, including circadian disruption, obesity, adverse lifestyle habits like physical inactivity and unhealthy food, and psychosocial influences like stress, loneliness, and low socioeconomic status.
“chronic sleep disturbances may be the cause or the consequence of other known triggers of low-grade inflammation, including circadian disruption (370), obesity (406), adverse lifestyle habits like physical inactivity (431) and unhealthy food (508), and psychosocial influences like stress (121, 189, 454, 525), loneliness (120), and low socioeconomic status (166)”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [406]
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The Sleep-Immune Crosstalk in Health and Disease
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- Authors
- Oishi, Y., Yoshida, K., Scammell, T. E., Urade, Y., Lazarus, M., & Saper, C. B.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- University of Tsukuba (JP)
- Corresponding author
- Lazarus, Michael
- Saper, Clifford B.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 47
- Pages
- 172-177
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC4468012
- OpenAlex
- W2088646411
- Cited by
- 34
- References
- 46
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 2
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- G. Harold and Leila Y. Mathers Foundation
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology
- Nestlé Nutrition Council, Japan (DK37097)
- National Institutes of Health (24300129, 25890005, NS072337)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Keywords
- prostaglandin E2, prostaglandin D2, lipopolysaccharide, NREM sleep, fever, body temperature, EP4 receptor, EP3 receptor, DP receptor, cyclooxygenase, meloxicam, sleep-wake behavior, neuroimmune interactions, bacterial infection
- MeSH terms
- Meloxicam, Animals, Body Temperature, Lipopolysaccharides, Sleep, Thiazines, Thiazoles, Prostaglandin D2, Dinoprostone, Cyclooxygenase Inhibitors, Mice, Knockout, Mice, Receptors, Prostaglandin E, EP3 Subtype, Receptors, Prostaglandin E, EP4 Subtype
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