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Sleep enhances IL‐6 trans‐signaling in humans
Abstract
Sleep is commonly considered to support immune defense. The underlying sleep‐immune interaction appears to rely critically on cytokines, like interleukin‐6 (IL‐6), that combine effects on immune and neuronal functions. The IL‐6 signal is conveyed in two ways: it stimulates a restricted group of (mostly immune) cells via membrane‐bound IL‐6 receptors (mIL‐6R) by forming a complex with soluble IL‐6R (sIL‐6R), and it stimulates (via membrane‐bound gp130) a great variety of other cell types—a process termed trans ‐signaling. Focusing on the receptor side of IL‐6 signaling, we examined the effect of sleep on sIL‐6R plasma concentrations, mIL‐6R expression, plasma sgp130, and numbers of IL‐6‐producing monocytes in healthy humans who were tested during a regular sleep‐wake cycle and 24 h of wakefulness while blood was sampled repeatedly. Sleep strongly enhanced concentrations of sIL‐6R, exceeding wake levels by 70% at the end of sleep. This rise was due to an increase in the PC (proteolytic cleavage) rather than the DS (differentially spliced) variant of sIL‐6R. Sleep did not affect IL‐6‐producing monocytes, mIL‐6R density, or sgp130 concentrations. The selective increase in sIL‐6R implicates an enhanced trans ‐signaling capacity whereby sleep distinctly widens the profile of IL‐6 actions, enabling an integrated influence on brain and peripheral organs.—Dimitrov, S., Lange, T., Benedict, C., Nowell, M. A., Jones, S. A., Scheller, J., Rose‐John, S., Born, J. Sleep enhances IL‐6 trans‐signaling in humans. FASEB J. 20, E1599 –E1609 (2006)
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In the citing paper
“Dimitrov et al (2006) have found that monocyte production of IL-6 also peaks at 0200 hours even in the midst of sleep deprivation.”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Dimitrov et al, 2006
In the citing paper
“Along with nocturnal increase in IL-6, there is a robust increase in circulating levels of IL-6R (Dimitrov and Lange et al, 2006).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Dimitrov and Lange et al, 2006
In the citing paper
“Similarly, total monocyte counts, lymphocyte counts, and the major lymphocyte subsets (i.e., B cells, CD4 and CD8 T cells, NK cells), have been found to be either reduced by sleep (46, 67, 148, 251, 254, 480, 556, 580) or unchanged (3, 69, 103, 122, 152, 178, 224, 234, 263, 338, 418, 463, 469) when compared with acute or prolonged sleep reduction in humans.”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [148]
In the citing paper
“sleep might rather support the migration of lymphocytes, thus supporting the formation of immunological memory.”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [148]
In the citing paper
“Sleep reduces the number of APCs and T cells in the blood, probably by redistributing these cells to lymph nodes (67, 143, 148, 169)”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [148]
In the citing paper
“In addition, sleep, by favoring pro-inflammatory and Th1 cytokine production, further supports the interaction between APCs and T cells and the subsequent differentiation and proliferation of Th1 cells, eventually leading to the formation of IgG1 and IgG3 antibodies (24, 67, 148, 254, 320).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [148]
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Metadata
- Authors
- Dimitrov, S., Lange, T., Benedict, C., Nowell, M. A., Jones, S. A., Scheller, J., Rose‐John, S., Born, J., Dimitrov, S., Lange, T., Benedict, C., Nowell, M. A., Jones, S. A., Scheller, J., Rose‐John, S., & Born, J.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2006-08-15
- Volume
- 20
- Issue
- 12
- Pages
- 2174-2176
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2089623849
- Semantic Scholar
- f57ab1a45668acdae5874b167770f0412c77ec30
- Cited by
- 115
- References
- 61
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 10 · 2023: 2 · 2022: 11 · 2021: 8 · 2020: 3 · 2019: 8 · 2018: 4 · 2017: 6 · 2016: 5 · 2015: 9 · 2014: 7 · 2013: 6 · 2012: 6
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep, interleukin-6, IL-6 trans-signaling, soluble IL-6 receptor, soluble gp130, sleep-wake cycle, cytokine signaling, sleep-immune interaction
- MeSH terms
- Adult, Humans, Male, Monocytes, Sleep, Solubility, Tissue Distribution, Signal Transduction, Interleukin-6, Cytokines, Receptors, Interleukin-6
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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