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Cited by 209Sleep and Wakefulness ResearchCircadian rhythm and melatoninSleep and Work-Related Fatigue

Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans

Dimitrov, Stoyan, Lange, Tanja, Tieken, Swantje, Fehm, Horst L, Born, Jan·2004·Brain, Behavior, and Immunity
DOI 10.1016/j.bbi.2003.08.004
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Abstract

Recent human studies suggested a supportive influence of regular nocturnal sleep on immune responses to experimental infection (vaccination). We hypothesized here that sleep could ease such responses by shifting the balance between T helper 1 (Th1) and T helper 2 (Th2) cytokine activity towards Th1 dominance thereby favoring cellular over humoral responses to infection. We compared the Th1/Th2 cytokine balance in 14 healthy men during regular nocturnal sleep (between 23:00 and 07:00 h) and while remaining awake during the same nocturnal interval, in a within-subject cross-over design. Blood was collected every 2 h. Production of T cell derived cytokines--interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha)--was measured at the single cell level using multiparametric flow cytometry. Also, several immunoactive hormones--prolactin, growth hormone (GH), thyroid stimulating hormone (TSH), cortisol, and melatonin--were measured, the release of which is known to be regulated by sleep. Compared with wakefulness, early nocturnal sleep induced a shift in the Th1/Th2 cytokine balance towards increased Th1 activity, as indicated by an increased (p <.05) ratio of IFN-gamma/IL-4 producing T helper cells. However, the Th1 shift was only of moderate size and replaced by Th2 dominance during late sleep (p <.05). It could be mediated via release of prolactin and GH which both were distinctly increased during sleep (p <.001). Though unexpected, the most pronounced effect of sleep on T cell cytokine production was a robust decrease in TNF-alpha producing CD8+ cells probably reflecting increased extravasation of cytotoxic effector and memory T cells.

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Crossref · 10.1016/j.bbi.2003.08.004

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  • Early nocturnal sleep increased the ratio in IFN-γ/IL-4 production by Th cells, indicating a shift in the Th1/Th2 cytokine balance towards preponderant production of Th1 cytokines.

    “Moreover, early nocturnal sleep increased the ratio in IFN-␥/IL-4 production by Th cells, indicating a shift in the Th1/Th2 cytokine balance towards preponderant production of Th1 cytokines (308).”

    From About Sleep's Role in Memory (2013) · cites this paper as [308]

  • In humans, early nocturnal SWS-rich sleep is associated with a shift towards Th1 cytokine activity predominating over Th2 activity which is replaced by a shift towards the predominance of Th2 cytokine production during late sleep when SWS is fading and REM sleep becomes prevalent.

    “Moreover, in humans, early nocturnal SWS-rich sleep is associated with a shift towards Th1 cytokine activity predominating over Th2 activity which is replaced by a shift towards the predominance of Th2 cytokine production during late sleep when SWS is fading and REM sleep becomes prevalent (308).”

    From About Sleep's Role in Memory (2013) · cites this paper as [308]

  • Recent data support a key role of gut microbiota and corresponding microbiota-derived PAMPs in central nervous processes like mood, cognition, pain, and eating behavior in animals, with first evidence for such a relationship in humans.

    “recent data support a key role of gut microbiota and corresponding microbiota-derived PAMPs in central nervous processes like mood, cognition, pain, and eating behavior in animals, and there is also first evidence for such a relationship in humans (85, 150, 151, 394).”

    From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [150]

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Authors
Dimitrov, S., Lange, T., Tieken, S., Fehm, H. L., & Born, J.
Affiliations
University of Lübeck (DE)
ORCID
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2004-07
Volume
18
Issue
4
Pages
341-348
ISSN
0889-1591 (ISSN-L)
DOI
10.1016/j.bbi.2003.08.004
OpenAlex
W2052097044
Cited by
209
References
41
Citations by year
2026: 8 · 2025: 14 · 2024: 16 · 2023: 6 · 2022: 16 · 2021: 7 · 2020: 9 · 2019: 10 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 9 · 2014: 11 · 2013: 8 · 2012: 10
FWCI
4.07
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
Keywords
sleep, Th1/Th2 balance, T helper cells, interferon-gamma, IL-4, interleukin-2, TNF-α, prolactin, growth hormone, melatonin, cortisol, thyroid-stimulating hormone, CD8+ T cells, nocturnal sleep, immune regulation
MeSH terms
Adult, Analysis of Variance, Circadian Rhythm, Flow Cytometry, Humans, Interferon-gamma, Interleukin-2, Male, Prolactin, Reference Values, Sleep, Sleep Deprivation, Thyrotropin, Tumor Necrosis Factor-alpha, Wakefulness, Interleukin-4, T-Lymphocyte Subsets, Th1 Cells, Th2 Cells, Cross-Over Studies, Lymphocyte Count, Human Growth Hormone

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