Effects of sleep and circadian rhythm on human circulating immune cells
Abstract
The role of nocturnal sleep for normal immune regulation and its relation to circadian rhythm was examined in 10 men participating in two 51-h sessions. One session included two regular wake-sleep cycles; the other included a night of sustained wakefulness followed by a night of recovery sleep. Blood was collected every 3 h to determine PBMC counts, including the enumeration of monocytes, NK cells, and lymphocyte subsets (CD19+, CD3+, CD4+, CD8+, HLA-DR+). Production of IL-1beta, TNF-alpha, IL-2, and IFN-gamma was determined after stimulation of whole blood samples with LPS and PHA, respectively. Concentrations of IL-6 and cortisol were assessed in plasma. Enumeration of cells indicated significant circadian rhythms for all PBMC subsets under conditions of sustained wakefulness. Compared with sustained wakefulness, nocturnal sleep acutely reduced the numbers of monocytes, NK cells, and counts of all lymphocyte subsets. However, in the afternoon and evening of the day following sleep, counts of NK cells and lymphocytes were significantly higher than after nocturnal wakefulness, indicating that effects of sleep interacted with those of the circadian pacemaker. Sleep markedly enhanced production of IL-2 by T cells (CD3+) but did not influence production of IL-1beta and TNF-alpha, or IL-6 concentrations. Effects of sleep were not mediated by changes in cortisol. The decrease in monocytes, NK cells, and lymphocytes, together with an increased production of IL-2 during sleep, may serve to support ongoing immune defense in extravascular lymphoid tissue during a time of diminished acute Ag challenge.
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Several reports indicated an enhancing influence of sleep on T-cell production of IL-2 which acts to further promote T-cell growth, proliferation, and differentiation, although other studies failed to reveal such effects when examining IL-2 production in specific T-cell subpopulations.
“Furthermore, several reports indicated an enhancing influence of sleep on T-cell production of IL-2 which acts to further promote T-cell growth, proliferation, and differentiation (120, 595), although other studies failed to reveal such effects when examining IL-2 production in specific T-cell subpopulations (109,308).”
From About Sleep's Role in Memory (2013) · cites this paper as [120]
Nocturnal increases in TNF and its soluble receptor appear to be driven primarily by circadian factors.
“nocturnal increases in another proinflammatory cytokine, TNF, and its soluble receptor appear to be driven primarily by circadian factors”
From Why Sleep Is Important for Health: A Psychoneuroimmunology Perspective (2015) · cites this paper as Born et al. 1997
Circadian factors play a predominant role in regulating the distribution of immune cells.
“Circadian factors play a predominant role in regulating the distribution of immune cells.”
From Why Sleep Is Important for Health: A Psychoneuroimmunology Perspective (2015) · cites this paper as Born et al. 1997
The relative distribution of most major lymphocyte subsets does not change in response to sleep loss, with the exception of decreases in the numbers and relative percentage of NK cells.
“the relative distribution of most major lymphocyte subsets does not change in response to sleep loss, with the exception of decreases in the numbers and relative percentage of NK cells”
From Why Sleep Is Important for Health: A Psychoneuroimmunology Perspective (2015) · cites this paper as Born et al. 1997
Both partial- and total-night sleep deprivation reduce T cell production of IL-2, and this effect is independent of the total number of circulating T cells.
“Both partial- and total-night sleep deprivation reduce T cell production of IL-2, and this effect is independent of the total number of circulating T cells”
From Why Sleep Is Important for Health: A Psychoneuroimmunology Perspective (2015) · cites this paper as Born et al. 1997
IL-6 displays a circadian rhythm, with a first peak around 2 am and a second peak around 5 am.
“IL-6 displays a circadian rhythm, with a first peak around 2 am and a second peak around 5 am (Fig. 2).82,83”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [82]
In 10 healthy, lean men, white blood cell counts peaked around 11 pm, decreased throughout the night and reached a nadir at 8 am.
“In 10 healthy, lean men, white blood cell counts peaked around 11 pm, decreased throughout the night and reached a nadir at 8 am.82”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [82]
TNF-α also displays a circadian rhythm, peaking close to the awakening (6 am) and reaching a nadir around 3 pm.
“TNF-α also displays a circadian rhythm, peaking close to the awakening (6 am) and reaching a nadir around 3 pm (Fig. 2).”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [82]
IL-1β decreases during the night and reaches its nadir at 8 am in the morning.
“IL-1β decreases during the night and reaches its nadir at 8 am in the morning.82”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [82]
IL-1β is elevated after partial and total sleep deprivation, but one study found no changes after total sleep deprivation.
“IL-1β was elevated after partial,106,112 and total sleep deprivation,96 but one study did not find any changes after total sleep deprivation82”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [82]
TNF-α levels are most often unchanged after partial sleep restriction, but not always.
“TNF-α levels are most often,82,93,112 but not always,107 unchanged after partial sleep restriction.”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [82]
Increased plasma IL-6 is reported after partial and total sleep deprivation in most cases, though two studies only reported loss of circadian rhythms.
“Increased plasma levels of IL-6 were reported after partial and total sleep deprivation in most cases,93,106,107,108,112 although two studies only reported a loss of circadian rhythms82,96”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [82]
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Nocturnal sleep uniformly reduces numbers of different T-cell subsets in the blood of healthy men
Besedovsky, L., Dimitrov, S., Born, J., & Lange, T. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00149.2016 · Cited by 32 · see citing works
Self-citationUtilization of Diurnal Rodents in the Research of Depression
Bilu, C., Einat, H., & Kronfeld‐Schor, N. (2016) · Drug Development Research · doi:10.1002/ddr.21346 · Cited by 32 · see citing works
Besedovsky, L., Linz, B., Born, J., & Lange, T. (2014) · European Journal of Immunology · doi:10.1002/eji.201344265 · Cited by 31 · see citing works
Self-citationSleep Deprivation Induces Changes in Immunity in <i>Trichinella spiralis</i> -Infected Rats
Ibarra-Coronado, E. G., Velazquéz-Moctezuma, J., Diaz, D., Becerril-Villanueva, L. E., Pavón, L., & Morales-Montor, J. (2015) · International Journal of Biological Sciences · doi:10.7150/ijbs.11907 · Cited by 30 · see citing works
Guariniello, L. D., Vicari, P., Lee, K. S., de Oliveira, A. C., & Tufik, S. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.22743 · Cited by 30 · see citing works
The immune recovery function of sleep – Tracked by neutrophil counts
Lange, T., & Born, J. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.08.008 · Cited by 30 · see citing works
Self-citationCross-Translational Studies in Human and Drosophila Identify Markers of Sleep Loss
Thimgan, M. S., Gottschalk, L., Toedebusch, C., McLeland, J., Rechtschaffen, A., Gilliland-Roberts, M., Duntley, S. P., & Shaw, P. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061016 · Cited by 26 · see citing works
Prather, A. A. (2019) · Sleep and Health · doi:10.1016/b978-0-12-815373-4.00024-1 · Cited by 27 · see citing works
Systemic immune parameters and sleep after ultra-low dose administration of IL-2 in healthy men
Lange, T., Marshall, L., Späth-Schwalbe, E., Fehm, H.-L., & Born, J. (2002) · Brain, Behavior, and Immunity · doi:10.1016/s0889-1591(02)00018-1 · Cited by 23 · see citing works
Self-citationBesedovsky, L., Born, J., & Lange, T. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.07.016 · Cited by 23 · see citing works
Self-citationIrwin, M. R., & Rinetti, G. (2004) · Alcohol · doi:10.1016/j.alcohol.2003.10.002 · Cited by 13 · see citing works
STRAUB, R. H., DEL REY, A., & BESEDOVSKY, H. O. (2007) · Psychoneuroimmunology · doi:10.1016/b978-012088576-3/50014-9 · Cited by 14 · see citing works
- Authors
- Born, J., Lange, T., Hansen, K., Mölle, M., & Fehm, H. L.
- Affiliations
- Clinical Neuroendocrinology, University of Lübeck ,
- University of Lübeck (DE)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-05-01
- Volume
- 158
- Issue
- 9
- Pages
- 4454-4464
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1592968073
- Cited by
- 611
- References
- 20
- Citations by year
- 2026: 14 · 2025: 27 · 2024: 27 · 2023: 28 · 2022: 31 · 2021: 25 · 2020: 34 · 2019: 26 · 2018: 18 · 2017: 31 · 2016: 33 · 2015: 25 · 2014: 15 · 2013: 27 · 2012: 19
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- sleep, circadian rhythm, immune regulation, peripheral blood mononuclear cells, monocytes, natural killer cells, lymphocyte subsets, interleukin-2, cytokine production, sustained wakefulness, cortisol, HLA-DR, T cells
- MeSH terms
- Adult, Affect, Body Temperature, Circadian Rhythm, Erythrocyte Count, Hematocrit, Hematopoiesis, Humans, Hydrocortisone, Immunity, Leukocyte Count, Male, Platelet Count, Sleep, Tissue Distribution, Cytokines
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