The DOI matches its Crossref record; 57 of the 58 references it cites were found in a registry or an index.
Effects of Sustained Sleep Restriction on Mitogen-Stimulated Cytokines, Chemokines and T Helper 1/ T Helper 2 Balance in Humans
Open accessAbstract
BACKGROUND: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. METHODS: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00-07.00 h) followed by 5 days with restricted sleep (03.00-07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-α), interleukin (IL) -1β, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed. RESULTS: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-α and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day. CONCLUSIONS: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.
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In the citing paper
“When appraised collectively, these studies show that sleep restriction increases afternoon cortisol: Table 2.”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [84]
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“the amount of SWS and REM sleep appears to be slightly, but significantly reduced”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [25]
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“Such PSG-derived sleep impairments are generally of a much lesser magnitude than subjectively reported sleep impairments. For example, total sleep time based on diary-based assessment is estimated to be 50 min less compared with PSG-based assessment”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [25]
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Cites
Atherosclerosis--an inflammatory disease
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Impact of sleep debt on metabolic and endocrine function
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Psychological stress and the human immune system: a meta-analytic study of 30 Years of inquiry
Segerstrom, S. C., & Miller, G. E. (2004) · Psychological Bulletin · doi:10.1037/0033-2909.130.4.601 · Cited by 3,334
Self-citationCappuccio, F. P., Cooper, D., D'Elia, L., Strazzullo, P., & Miller, M. A. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr007 · Cited by 2,146
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Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk
Meier-Ewert, H. K., Ridker, P. M., Rifai, N., Regan, M. M., Price, N. J., Dinges, D. F., & Mullington, J. M. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.07.050 · Cited by 1,195
Adverse Effects of Modest Sleep Restriction on Sleepiness, Performance, and Inflammatory Cytokines
Vgontzas, A. N., Zoumakis, E., Bixler, E. O., Lin, H.-M., Follett, H., Kales, A., & Chrousos, G. P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031562 · Cited by 1,050
Spiegel, K., Leproult, R., L’Hermite-Balériaux, M., Copinschi, G., Penev, P. D., & Van Cauter, E. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1003 · Cited by 1,006
A circadian clock in macrophages controls inflammatory immune responses
Keller, M., Mazuch, J., Abraham, U., Eom, G. D., Herzog, E. D., Volk, H.-D., Kramer, A., & Maier, B. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906361106 · Cited by 843 · cited 1×
“In general, immune responses show strong diurnal rhythms [33], and the mechanisms seem to include sleep dependent aspects (via prolactin), the circadian system (via cortisol) as well as the numbers of natural regulatory T cells and the internal circadian clocks of macrophages [34,35].”
A sthma : Mechanisms of Disease Persistence and Progression
Cohn, L. E., Elias, J. A., & Chupp, G. L. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104716 · Cited by 821
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Zhao, F., Li, Y., Zhou, Y., Fu, E., Zhu, S., Yu, L., Xu, H., Li, Q., Li, Q., Zhang, P., et al. (2026) · Patient Preference and Adherence · doi:10.2147/ppa.s608376
A crosstalk between the immune system and obstructive sleep apnea
Ahmed, S., Gozal, D., Borthakur, A., & Khalyfa, A. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1963127
Metadata
- Authors
- Axelsson, J., Rehman, J.-U., Akerstedt, T., Ekman, R., Miller, G. E., Höglund, C. O., & Lekander, M.
- Affiliations
- Stockholm University (SE)
- Karolinska Institutet (SE)
- University of Gothenburg (SE)
- University of British Columbia (CA)
- Karolinska University Hospital (SE)
- Corresponding author
- Axelsson, John
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-12-11
- Volume
- 8
- Issue
- 12
- Pages
- e82291
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3859577
- OpenAlex
- W1974452187
- Cited by
- 103
- References
- 56
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 5 · 2023: 9 · 2022: 12 · 2021: 13 · 2020: 10 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 9 · 2014: 9
- FWCI
- 10.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Sleep Research Society
- Svenska Sällskapet för Medicinsk Forskning
- Astma- och Allergiförbundet
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep restriction, sleep deprivation, Th1/Th2 balance, cytokines, chemokines, interleukin-2, IL-4, TNF-α, MCP-1, phytohemagglutinin, cell-mediated immunity, circadian variation, cortisol, allergic diseases, asthma
- MeSH terms
- Adult, Humans, Hydrocortisone, Leukocyte Count, Male, Mitogens, Phytohemagglutinins, Sleep Deprivation, Th1 Cells, Th2 Cells, Chemokines, Young Adult, Th1-Th2 Balance
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