Immune Outcomes of Paradoxical Sleep Deprivation on Cellular Distribution in Naive and Lipopolysaccharide-Stimulated Mice
Abstract
Background/Aims: Several lines of evidence indicate that sleep loss imposes significant consequences on the host defense system, including changes in cell number, activity and distribution. However, it is not clear whether cellular alterations after sleep deprivation are caused by redistribution to immune organs or by death of these cells or how the response to a nonspecific immune activator would be affected. Therefore, the aim of this study was to assess the leukocyte distribution after paradoxical sleep deprivation (PSD) in saline- and lipopolysaccharide-treated mice. Methods: Adult inbred mice were paradoxical sleep deprived (72 h), whereas the controls were kept in their home cages. After PSD, both groups received an injection of either saline or lipopolysaccharide (LPS; 1 or 5 µg/animal, intraperitoneally), 2 h prior to the collection of blood, spleen, lymph nodes and peritoneal wash. Isolated cells were then designated to differential leukocyte count (blood) and flow cytometry analysis of immune cell subsets (immune sites). Results: The data revealed that PSD caused a significant reduction of circulating lymphocytes and a general decrease in all cellular subsets of spleen, mainly T and B cells. However, no alteration in response of PSD was found on other immune sites, such as lymph nodes and peritoneum. Of note, immune cell distribution in response to in vivo LPS stimulation remained unchanged after PSD. Conclusions: Our study provided original evidence concerning the immune outcomes of PSD, indicating that cellular decrease caused by PSD is not restricted to circulation, but also to immune sites. Taken together, our results could help shed light on the physiological mechanisms of leukocyte trafficking.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In rats undergoing prolonged sleep restriction for 21 consecutive days, a decrease in total leukocyte counts normalized after 24 h of recovery sleep, but did not normalize after recovery sleep following a REM sleep deprivation protocol over 4 consecutive days.
“In rats undergoing prolonged sleep restriction for 21 consecutive days, a decrease in total leukocyte counts normalized after 24 h of recovery sleep, but did not normalize after recovery sleep following a REM sleep deprivation protocol over 4 consecutive days (596).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [596]
Cites
Dhabhar, F. S., & McEwen, B. S. (1997) · Brain Behavior and Immunity · doi:10.1006/brbi.1997.0508 · Cited by 1,014 · see citing works
Metabolic consequences of sleep and sleep loss
Van Cauter, E., Spiegel, K., Tasali, E., & Leproult, R. (2008) · Sleep Medicine · doi:10.1016/s1389-9457(08)70013-3 · Cited by 812 · see citing works
Grandner, M. A., Hale, L., Moore, M., & Patel, N. P. (2010) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2009.07.006 · Cited by 602 · see citing works
Sick and tired: does sleep have a vital role in the immune system?
Bryant, P. A., Trinder, J., & Curtis, N. (2004) · Nature Reviews Immunology · doi:10.1038/nri1369 · Cited by 551 · see citing works
Machado, R. B., Hipólide, D. C., Benedito‐Silva, A. A., & Tufik, S. (2004) · Brain Research · doi:10.1016/j.brainres.2004.01.019 · Cited by 424 · see citing works
Self-citationDinges, D. F., Douglas, S. D., Zaugg, L., Campbell, D. E., McMann, J. M., Whitehouse, W. G., Orne, E. C., Kapoor, S. C., Icaza, E., & Orne, M. T. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117184 · Cited by 361 · see citing works
Sleep Enhances the Human Antibody Response to Hepatitis A Vaccination
Lange, T., Perras, B., Fehm, H. L., & Born, J. (2003) · Psychosomatic Medicine · doi:10.1097/01.psy.0000091382.61178.f1 · Cited by 351 · see citing works
Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice
Silva, R. H., Abílio, V. C., Takatsu, A. L., Kameda, S. R., Grassl, C., Chehin, A. B., Medrano, W. A., Calzavara, M. B., Registro, S., Andersen, M. L., et al. (2004) · Neuropharmacology · doi:10.1016/j.neuropharm.2003.11.032 · Cited by 307 · see citing works
Self-citationDhabhar, F. S. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb05454.x · Cited by 279 · see citing works
Sustained sleep deprivation impairs host defense
Everson, C. A. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.265.5.r1148 · Cited by 251 · see citing works
Partial sleep deprivation reduces natural killer cell activity in humans.
Irwin, M., Mascovich, A., Gillin, J. C., Willoughby, R., Pike, J., & Smith, T. L. (1994) · Psychosomatic Medicine · doi:10.1097/00006842-199411000-00004 · Cited by 249 · see citing works
Systemic bacterial invasion induced by sleep deprivation
Everson, C. A., & Toth, L. A. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.278.4.r905 · Cited by 248 · see citing works
Andersen, M. L., Martins, P. J. F., D’Almeida, V., Bignotto, M., & Tufik, S. (2005) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2004.00428.x · Cited by 246 · see citing works
Self-citationDose-dependent effects of endotoxin on human sleep
Mullington, J., Korth, C., Hermann, D. M., Orth, A., Galanos, C., Holsboer, F., & Pollmächer, T. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.278.4.r947 · Cited by 226 · see citing works
Effects of acute and chronic sleep loss on immune modulation of rats
Zager, A., Andersen, M. L., Ruiz, F. S., Antunes, I. B., & Tufik, S. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00105.2007 · Cited by 200 · see citing works
Self-citationBøyum, A., Wiik, P., Gustavsson, E., Veiby, O. P., Reseland, J. E., Haugen, A.-H., & Opstad, P. K. (1996) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.1996.d01-32.x · Cited by 153 · see citing works
Lorton, D., Lubahn, C. L., Estus, C., Millar, B. A., Carter, J. L., Wood, C. A., & Bellinger, D. L. (2006) · NeuroImmunoModulation · doi:10.1159/000104864 · Cited by 147 · see citing works
Everson, C. A. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00021.2005 · Cited by 141 · see citing works
Enhancement of slow-wave sleep by endotoxin and lipid A
Krueger, J. M., Kubillus, S. L., Shoham, S., & Davenne, D. (1986) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1986.251.3.r591 · Cited by 124 · see citing works
(1989) · PubMed · Cited by 99 · see citing works
Morrow, J. D., & Opp, M. R. (2004) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2004.04.001 · Cited by 94 · see citing works
Opp, M. R., & Toth, L. A. (1998) · Life Sciences · doi:10.1016/s0024-3205(98)00010-1 · Cited by 93 · see citing works
Neuroimmune Interactions in Stress
Costa‐Pinto, F. A., & Palermo‐Neto, J. (2010) · NeuroImmunoModulation · doi:10.1159/000258722 · Cited by 87 · see citing works
Effects of 48 hours sleep deprivation on human immune profile.
Öztürk, L., Pelin, Z., Karadeniz, D., Kaynak, H., Cakar, L., & Gözükırmızı, E. (1999) · PubMed · Cited by 86 · see citing works
Zager, A., Andersen, M. L., Lima, M. M. S., Reksidler, A. B., Machado, R. B., & Tufik, S. (2009) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2009.03.005 · Cited by 63 · see citing works
Self-citationViveros-Paredes, J. M., Puebla-Pérez, A. M., Gutiérrez-Coronado, O., Sandoval-Ramírez, L., & Villaseñor-García, M. M. (2006) · International Immunopharmacology · doi:10.1016/j.intimp.2005.11.011 · Cited by 62 · see citing works
Ruiz, F. S., Andersen, M. L., Zager, A., Martins, R. C. S., & Tufik, S. (2007) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2006005000086 · Cited by 51 · see citing works
Self-citationEffects of Sleep on Endotoxin-Induced Host Responses in Healthy Men
Haack, M., Schuld, A., Kraus, T., & Pollmächer, T. (2001) · Psychosomatic Medicine · doi:10.1097/00006842-200107000-00008 · Cited by 44 · see citing works
Renegar, K. B., Crouse, D., Floyd, R. A., & Krueger, J. (2000) · Sleep · doi:10.1093/sleep/23.7.1 · Cited by 38 · see citing works
Everson, C. A., Thalacker, C. D., & Hogg, N. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90623.2008 · Cited by 35 · see citing works
Gundersen, Y., Opstad, P. K., Reistad, T., Thrane, I., & Vaagenes, P. (2006) · European Journal of Applied Physiology · doi:10.1007/s00421-006-0150-8 · Cited by 34 · see citing works
Pruett, S. B., Fan, R., & Zheng, Q. (2003) · International Immunopharmacology · doi:10.1016/s1567-5769(02)00081-4 · Cited by 31 · see citing works
Velázquez‐Moctezuma, J., Domı́nguez-Salazar, E., Barberena, E. C., Nájera-Medina, O., Retana‐Márquez, S., Rodríguez-Aguilera, E., Jiménez‐Anguiano, A., Cortes-Martinez, L., & Ortiz, R. (2004) · NeuroImmunoModulation · doi:10.1159/000078445 · Cited by 26 · see citing works
Palma, B. D., & Tufik, S. (2010) · SLEEP · doi:10.1093/sleep/33.9.1244 · Cited by 24 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The Sleep-Immune Crosstalk in Health and Disease
Besedovsky, L., Lange, T., & Haack, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00010.2018 · Cited by 1,479 · see citing works
Sleep Loss and Cytokines Levels in an Experimental Model of Psoriasis
Hirotsu, C., Rydlewski, M., Araújo, M. S., Tufik, S., & Andersen, M. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051183 · Cited by 103 · see citing works
Self-citationSleep-deprivation reduces NK cell number and function mediated by β-adrenergic signalling
De Lorenzo, B. H. P., de Oliveira Marchioro, L., Greco, C. R., & Suchecki, D. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.04.006 · Cited by 85 · see citing works
Arthaud, S., Varin, C., Gay, N., Libourel, P., Chauveau, F., Fort, P., Luppi, P., & Peyron, C. (2014) · Journal of Sleep Research · doi:10.1111/jsr.12269 · Cited by 58 · see citing works
Chronic Sleep Restriction Impairs the Antitumor Immune Response in Mice
Lorenzo, B. H. P. D., Brito, R. R. N. E., Leal, T. P., Garcia, N. P., dos Santos, R. M. M., Alvares-Saraiva, A. M., Hurtado, E. C. P., dos Reis, T. C. B., & Palma, B. D. (2018) · NeuroImmunoModulation · doi:10.1159/000490352 · Cited by 58 · see citing works
Hazards of insomnia and the effects of acupuncture treatment on insomnia
Lin, Y.-F., Liu, Z., Ma, W., & Shen, W.-D. (2016) · Journal of Chinese Integrative Medicine · doi:10.1016/s2095-4964(16)60248-0 · Cited by 45 · see citing works
Pellegrino, R., Sunaga, D. Y., Guindalini, C., Martins, R. C. S., Mazzotti, D. R., Wei, Z., Daye, Z. J., Andersen, M. L., & Tufik, S. (2012) · Physiological Genomics · doi:10.1152/physiolgenomics.00058.2012 · Cited by 42 · see citing works
Self-citationHuang, J., Song, P., Hang, K., Chen, Z.-K., Zhu, Z., Zhang, Y., Xu, J., Qin, J., Wang, B., Qu, W., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.727959 · Cited by 42 · see citing works
Ruiz, F. S., Andersen, M. L., Guindalini, C., Araújo, L. P., Lopes, J. D., & Tufik, S. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.12.027 · Cited by 31 · see citing works
Self-citationSleep enhances numbers and function of monocytes and improves bacterial infection outcome in mice
Hahn, J. K., Günter, M., Schuhmacher, J., Bieber, K., Pöschel, S., Schütz, M., Engelhardt, B., Oster, H., Sina, C., Lange, T., et al. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.01.001 · Cited by 23 · see citing works
Ashley, N. T., Walton, J. C., Haim, A., Zhang, N., Prince, L. A., Fruchey, A. M., Lieberman, R. A., Weil, Z. M., Magalang, U. J., & Nelson, R. J. (2013) · Journal of Experimental Biology · doi:10.1242/jeb.083832 · Cited by 20 · see citing works
Hypocretin/orexin loss changes the hypothalamic immune response
Tanaka, S., Takizawa, N., Honda, Y., Koike, T., Oe, S., Toyoda, H., Kodama, T., & Yamada, H. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.06.009 · Cited by 15 · see citing works
Sleep Deprivation Alters the Pituitary Stress Transcriptome in Male and Female Mice
Oyola, M. G., Shupe, E. A., Soltis, A. R., Sukumar, G., Páez-Pereda, M., Larco, D. O., Wilkerson, M. D., Rothwell, S. W., Dalgard, C. L., & Wu, T. J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00676 · Cited by 14 · see citing works
The dual effect of paradoxical sleep deprivation on murine immune functions
Sá-Nunes, A., Bizzarro, B., Egydio, F., Barros, M. S., Sesti-Costa, R., Soares, E. M., Pina, A., Russo, M., Faccioli, L. H., Tufik, S., et al. (2016) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2015.11.013 · Cited by 11 · see citing works
Self-citationKurien, P. A., Chong, S. C., Ptáček, L. J., & Fu, Y. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.04.014 · Cited by 11 · see citing works
Walker, W. E. (2022) · Shock · doi:10.1097/shk.0000000000001976 · Cited by 8 · see citing works
Sleep disorders in hepatocellular carcinoma
Qian, J., Ruan, M., Wang, Z., Dong, W., Jia, J.-H., Feng, X.-C., & Liu, H. (2025) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v17.i10.110503 · Cited by 5 · see citing works
Zaytseva, D., Allawala, A. B., Franco, J. A., Putnam, S., Abtahie, A. M., Bubalo, N., Criddle, C. R., Nguyen, T. A., Nguyen, P., Padmanabhan, S., et al. (2018) · Physiological Reports · doi:10.14814/phy2.13812 · Cited by 3 · see citing works
Sleep deprivation silently undermines immunity
Zhou, Q., Feng, C., Li, S., Zhangyan, M., & Sun, Y. (2025) · International Journal of Surgery · doi:10.1097/js9.0000000000004071 · Cited by 2 · see citing works
Chronic sleep loss alters the inflammatory response and BDNF expression in C57BL/6J mice
Brice, K. N., Braden-Kuhle, P. N., Miller, S. K., Regan, A., Lacy, V. A., Chumley, M. J., & Boehm, G. W. (2024) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2024.578462 · Cited by 2 · see citing works
Neuro-inflammatory Response and Immune–Brain Crosstalk in Sleep Regulation
Jha, P. K., & Bouâouda, H. (2024) · Progress in inflammation research · doi:10.1007/978-3-031-74744-1_5 · Cited by 1 · see citing works
Autonomous or Integrated Immune System is Right for Biology?
Berczi, I. (2014) · Advances in Neuroimmune Biology · doi:10.3233/nib-140098
Berczi, I. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801770-8.00012-4
Wang, Y., Hu, Y., Wang, P., Hu, R., Chen, Z. Q., Zhang, T., Liu, J., Noda, M., Long, J., & Peng, Y. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26083485
- Authors
- Zager, A., Ruiz, F. S., Tufik, S., & Andersen, M. L.
- Affiliations
- Universidade Federal de São Paulo (BR)
- Venue
- Neuroimmunomodulation
- Publisher
- S. Karger AG
- Published
- 2012
- Volume
- 19
- Issue
- 2
- Pages
- 79-87
- ISSN
- 1021-7401 (ISSN-L)
- 1423-0216
- OpenAlex
- W2009202072
- Cited by
- 24
- References
- 35
- Citations by year
- 2025: 3 · 2024: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImmunoModulation (publishedVersion)
- PubMed (publishedVersion)
- UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- REM sleep deprivation, sleep deprivation, immune cell distribution, leukocyte migration, lipopolysaccharide, lymphocyte depletion, T cells, B cells, spleen, lymph nodes, peritoneal lavage, innate immune response, mice
- MeSH terms
- Animals, Immunity, Cellular, Leukocyte Count, Leukocytes, Lipopolysaccharides, Male, Mice, Inbred C57BL, Sleep Deprivation, Sleep, REM, Mice
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 ›
Are you an author, or do you see a problem with this page? Request a review