How (and why) the immune system makes us sleep
Open accessAbstract
Good sleep is necessary for physical and mental health. For example, sleep loss impairs immune function, and sleep is altered during infection. Immune signalling molecules are present in the healthy brain, where they interact with neurochemical systems to contribute to the regulation of normal sleep. Animal studies have shown that interactions between immune signalling molecules (such as the cytokine interleukin 1) and brain neurochemical systems (such as the serotonin system) are amplified during infection, indicating that these interactions might underlie the changes in sleep that occur during infection. Why should the immune system cause us to sleep differently when we are sick? We propose that the alterations in sleep architecture during infection are exquisitely tailored to support the generation of fever, which in turn imparts survival value.
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The proinflammatory cytokines IL-1, TNF-α, and IL-6 display a circadian pattern of secretion with peak levels correlating with feelings of sleepiness and sleep onset.
“The proinflammatory cytokines IL-1, TNF-α, and IL-6 display a circadian pattern of secretion with peak levels correlating with feelings of sleepiness and sleep onset (Imeri and Opp, 2009; Vgontzas et al., 2005).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Imeri and Opp, 2009
Changes in sleep during immune challenge are an actively driven process that facilitates fever production.
“changes in sleep during immune challenge is an actively driven process that facilitates the production of fever”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Imeri and Opp, 2009
There is a growing literature demonstrating direct effects of IL-1 and TNF on neural substrates implicated in the regulation of sleep.
“There is a growing literature demonstrating direct effects of IL-1 and TNF on neural substrates implicated in the regulation of sleep (reviewed by Imeri and Opp (2009)).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Imeri and Opp, 2009
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References 137 · Cited by 710
Research works printed but not linked: 2
- [19]Opp M Born J Irwin M Ader R Psychoneuroimmunology 579 618 Burlington, Massachusetts Elsevier Academic Press 2007
- [124]Nagasaki H Iriki M Inoue S Uchizono K Proceedings: Sleep promoting substances in the brain stem of rats Nippon Seirigaku Zasshi 36 293 1974 4377429
- Authors
- Imeri, L., & Opp, M. R.
- Affiliations
- University of Milan (IT)
- University of Michigan (US)
- Corresponding author
- Opp, Mark R.
- Venue
- Nature Reviews Neuroscience
- Published
- 2009-02-11
- Volume
- 10
- Issue
- 3
- Pages
- 199-210
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- PMC
- PMC2839418
- OpenAlex
- W2090466892
- Cited by
- 710
- References
- 137
- Citations by year
- 2026: 29 · 2025: 59 · 2024: 57 · 2023: 43 · 2022: 45 · 2021: 53 · 2020: 45 · 2019: 52 · 2018: 43 · 2017: 37 · 2016: 29 · 2015: 38 · 2014: 39 · 2013: 32 · 2012: 37
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Funders
- University of Michigan
- National Institutes of Health
- Medical School, University of Michigan
- National Heart, Lung, and Blood Institute (R01HL080972, HL080972)
- National Institute of Mental Health (R56MH064843, MH-64843, R01MH064843)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- sleep regulation, cytokines, serotonergic system, interleukin-1, infection, sickness behavior, sleep architecture, fever
- MeSH terms
- Animals, Brain, Fever, Humans, Immune System, Immunity, Innate, Infections, Serotonin, Sleep, Cytokines
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