Advertisement

Sleep and Breathing

, Volume 23, Issue 4, pp 1331–1339 | Cite as

Sleep deprivation alters neutrophil functions and levels of Th1-related chemokines and CD4+ T cells in the blood

  • Elias A. SaidEmail author
  • Mohammed A. Al-Abri
  • Iman Al-Saidi
  • Mohammed S. Al-Balushi
  • Jumaa Z. Al-Busaidi
  • Iman Al-Reesi
  • Crystal Y. Koh
  • Mohamed A. Idris
  • Ali A. Al-Jabri
  • Omar Habbal
Basic Science • Original Article

Abstract

Purpose

The state of knowledge about the effect of sleep deprivation on the immune system is scarce and conflicting. It would therefore be useful to investigate the consequences of sleep deprivation on the immune system. We have studied the effect of sleep deprivation on the changes in neutrophil functions, and the ex vivo proliferative pattern of CD4+ T lymphocytes in relationship with blood cytokine and chemokine levels due to the crucial role of these cells in mounting potent immune responses.

Methods

Healthy volunteers were followed for 3 weeks. They had normal sleep in weeks 1 and 3 and they were sleep-deprived on week 2, sleeping < 6 h per 24 h, a pattern similar to sleep behaviors of many chronically sleep-deprived individuals. We assessed the levels of Th1/Th2 and inflammatory cytokines and chemokines, CD4+ T cells, and the NADPH oxidase activation and phagocytic functions in neutrophils.

Results

Our results suggest that sleep deprivation leads to a decreased neutrophil capacity to phagocytose bacteria and activate NADPH oxidase (p < 0.05). Sleep deprivation was associated with a potential increase in CXCL9 levels and decrease in CXCL10/CXCL9 and CCL5/CXCL9 ratios (p < 0.05). Furthermore, our results suggest that the decrease in CD4+ T cell due to sleep deprivation was not associated with changes in their proliferation as observed by Ki67 levels, but rather, it correlated with changes in CXCL10/CXCL9 ratio (p < 0.05).

Conclusions

Sleep deprivation may lead to a decreased phagocytosis and NADPH oxidase activity in neutrophils and a decrease in the levels of CD4+ T cells which is related to changes in the Th1-related chemokine balance.

Keywords

Neutrophils Chemokines CXCL9 CXCL10 CCL5 CD4+ T cells Sleep deprivation 

Notes

Acknowledgments

We would like to thank the staff of the Microbiology and Immunology and Anatomy Departments in the College of Medicine and Health Sciences, Sultan Qaboos University, and the staff of the Sleep Medicine Unit in Sultan Qaboos University Hospital (SQUH).

Author contributions

EAS, MAA, and OH designed the project, performed some experiments, and participated in data analysis and manuscript writing. IS, MSB, JZB, and IR performed experiments and participated in the manuscript writing. CYK, MAI, and AAJ participated in data analysis and writing the manuscript.

Funding information

This study was supported by the College of Medicine and Health Sciences, Sultan Qaboos University (grant # IG/MED/ANAT/13/01).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Ethical considerations

All volunteers were informed about this study and signed an informed consent form. This study was approved by the Ethical Committee of the College of Medicine and Health Sciences in the Sultan Qaboos University (SQU), Oman. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

  1. 1.
    Knutson KL, Van Cauter E, Rathouz PJ, DeLeire T, Lauderdale DS (2010) Trends in the prevalence of short sleepers in the USA: 1975-2006. Sleep 33(1):37–45CrossRefGoogle Scholar
  2. 2.
    (CDC) CfDCaP (2017) Short sleep duration among US adults. National Center for Chronic Disease Prevention and Health Promotion, Division of Population Health (Data and Statistics). https://www.cdc.gov/sleep/data_statistics.html
  3. 3.
    Christoffersson G, Vagesjo E, Pettersson US, Massena S, Nilsson EK, Broman JE, Schioth HB, Benedict C, Phillipson M (2014) Acute sleep deprivation in healthy young men: impact on population diversity and function of circulating neutrophils. Brain Behav Immun 41:162–172.  https://doi.org/10.1016/j.bbi.2014.05.010 CrossRefPubMedGoogle Scholar
  4. 4.
    Dinges DF, Douglas SD, Zaugg L, Campbell DE, Mcmann JM, Whitehouse WG, Orne EC, Kapoor SC, Icaza E, Orne MT (1994) Leukocytosis and natural-killer-cell function parallel neurobehavioral fatigue-induced by 64 hours of sleep-deprivation. J Clin Invest 93(5):1930–1939.  https://doi.org/10.1172/Jci117184 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Hurtado-Alvarado G, Pavón L, Castillo-García SA, Hernández ME, Domínguez-Salazar E, Velázquez-Moctezuma J, Gómez-González B (2013) Sleep loss as a factor to induce cellular and molecular inflammatory variations. Clinical and Dev Immunol 2013:14.  https://doi.org/10.1155/2013/801341 CrossRefGoogle Scholar
  6. 6.
    Palmblad J, Petrini B, Wasserman J, Åkerstedt T (1979) Lymphocyte and granulocyte reactions during sleep deprivation. Psychosom Med 41(4):273–278CrossRefGoogle Scholar
  7. 7.
    Wilder-Smith A, Mustafa FB, Earnest A, Gen L, MacAry PA (2013) Impact of partial sleep deprivation on immune markers. Sleep Med 14(10):1031–1034.  https://doi.org/10.1016/j.sleep.2013.07.001 CrossRefPubMedGoogle Scholar
  8. 8.
    Bollinger T, Bollinger A, Skrum L, Dimitrov S, Lange T, Solbach W (2009) Sleep-dependent activity of T cells and regulatory T cells. Clin Exp Immunol 155(2):231–238.  https://doi.org/10.1111/j.1365-2249.2008.03822.x CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Axelsson J, Rehman JU, Akerstedt T, Ekman R, Miller GE, Hoglund CO, Lekander M (2013) Effects of sustained sleep restriction on mitogen-stimulated cytokines, chemokines and T helper 1/T helper 2 balance in humans. Plos One 8(12):UNSP e82291.  https://doi.org/10.1371/journal.pone.0082291 CrossRefGoogle Scholar
  10. 10.
    Voderholzer U, Fiebich BL, Dersch R, Feige B, Piosczyk H, Kopasz M, Riemann D, Lieb K (2012) Effects of sleep deprivation on nocturnal cytokine concentrations in depressed patients and healthy control subjects. J Neuropsych Clin N 24(3):354–366CrossRefGoogle Scholar
  11. 11.
    Abedelmalek S, Souissi N, Chtourou H, Denguezli M, Aouichaoui C, Ajina M, Aloui A, Dogui M, Haddouk S, Tabka Z (2013) Effects of partial sleep deprivation on proinflammatory cytokines, growth hormone, and steroid hormone concentrations during repeated brief sprint interval exercise. Chronobiol Int 30(4):502–509.  https://doi.org/10.3109/07420528.2012.742102 CrossRefPubMedGoogle Scholar
  12. 12.
    Redwine L, Hauger RL, Gillin JC, Irwin M (2000) Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans. J Clin Endocr Metab 85(10):3597–3603.  https://doi.org/10.1210/jc.85.10.3597 CrossRefPubMedGoogle Scholar
  13. 13.
    Wright KP, Drake AL, Frey DJ, Fleshner M, Desouza CA, Gronfier C, Czeisler CA (2015) Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance. Brain Behav Immun 47:24–34.  https://doi.org/10.1016/j.bbi.2015.01.004 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Trautmann L, Said EA, Halwani R, Janbazian L, Chomont N, El-Far M, Breton G, Haddad EK, Sekaly RP (2007) Programmed death 1: a critical regulator of T-cell function and a strong target for immunotherapies for chronic viral infections. Curr Opin HIV AIDS 2(3):219–227.  https://doi.org/10.1097/COH.0b013e3280ebb5c9 CrossRefPubMedGoogle Scholar
  15. 15.
    Said EA, Al-Yafei F, Zadjali F, Hasson SS, Al-Balushi MS, Al-Mahruqi S, Koh CY, Al-Naamani K, Al-Busaidi JZ, Idris MA, Balkhair A, Al-Jabri AA (2014) Association of single-nucleotide polymorphisms in TLR7 (Gln11Leu) and TLR9 (1635A/G) with a higher CD4T cell count during HIV infection. Immunol Lett 160(1):58–64.  https://doi.org/10.1016/j.imlet.2014.04.005 CrossRefPubMedGoogle Scholar
  16. 16.
    Mocsai A (2013) Diverse novel functions of neutrophils in immunity, inflammation, and beyond. J Exp Med 210(7):1283–1299.  https://doi.org/10.1084/jem.20122220 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    American Academy of Sleep Medicine A (2008) Sleep deprivation. American Academy of Sleep Medicine. http://www.aasmnet.org/resources/factsheets/sleepdeprivation.pdf. Accessed 30.06.2016
  18. 18.
    Nogueira LG, Santos RHB, Ianni BM, Fiorelli AI, Mairena EC, Benvenuti LA, Frade A, Donadi E, Dias F, Saba B, Wang HTL, Fragata A, Sampaio M, Hirata MH, Buck P, Mady C, Bocchi EA, Stolf NA, Kalil J, Cunha-Neto E (2012) Myocardial chemokine expression and intensity of myocarditis in Chagas cardiomyopathy are controlled by polymorphisms in CXCL9 and CXCL10. Plos Neglect Trop D 6(10):ARTN e1867.  https://doi.org/10.1371/journal.pntd.0001867 CrossRefGoogle Scholar
  19. 19.
    Said EA, Al-Abri MA, Al-Saidi I, Al-Balushi MS, Al-Busaidi JZ, Al-Reesi I, Koh CY, Hasson SS, Idris MA, Al-Jabri AA, Habbal O (2017) Altered blood cytokines, CD4 T cells, NK and neutrophils in patients with obstructive sleep apnea. Immunol Lett 190:272–278.  https://doi.org/10.1016/j.imlet.2017.08.009 CrossRefPubMedGoogle Scholar
  20. 20.
    Inwald EC, Klinkhammer-Schalke M, Hofstadter F, Zeman F, Koller M, Gerstenhauer M, Ortmann O (2013) Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Tr 139(2):539–552.  https://doi.org/10.1007/s10549-013-2560-8 CrossRefGoogle Scholar
  21. 21.
    Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER (2010) Neutrophil kinetics in health and disease. Trends Immunol 31(8):318–324.  https://doi.org/10.1016/j.it.2010.05.006 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Ochiai E, Sa QL, Brogli M, Kudo T, Wang XS, Dubey JP, Suzukit Y (2015) CXCL9 is important for recruiting immune T cells into the brain and inducing an accumulation of the T cells to the areas of tachyzoite proliferation to prevent reactivation of chronic cerebral infection with Toxoplasma gondii. Am J Pathol 185(2):314–324.  https://doi.org/10.1016/j.ajpath.2014.10.003 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Marshall A, Celentano A, Cirillo N, McCullough M, Porter S (2017) Tissue-specific regulation of CXCL9/10/11 chemokines in keratinocytes: implications for oral inflammatory disease. Plos One 12(3):ARTN e0172821.  https://doi.org/10.1371/journal.pone.0172821 CrossRefGoogle Scholar
  24. 24.
    He JY, Hsuchou H, He Y, Kastin AJ, Wang YP, Pan WH (2014) Sleep restriction impairs blood-brain barrier function. J Neurosci 34(44):14697–14706.  https://doi.org/10.1523/Jneurosci.2111-14.2014 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Menke J, Zeller GC, Kikawada E, Means TK, Huang XR, Lan HY, Lu B, Farber J, Luster AD, Kelley VR (2008) CXCL9, but not CXCL10, promotes CXCR3-dependent immune-mediated kidney disease. J Am Soc Nephrol 19(6):1177–1189.  https://doi.org/10.1681/Asn.2007111179 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Rosenblum JM, Shimoda N, Schenk AD, Zhang H, Kish DD, Keslar K, Farber JM, Fairchild RL (2010) CXC chemokine ligand (CXCL) 9 and CXCL10 are antagonistic costimulation molecules during the priming of alloreactive T cell effectors. J Immunol 184(7):3450–3460.  https://doi.org/10.4049/jimmunol.0903831 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lange T, Dimitrov S, Born J (2010) Effects of sleep and circadian rhythm on the human immune system. Ann N Y Acad Sci 1193:48–59.  https://doi.org/10.1111/j.1749-6632.2009.05300.x CrossRefPubMedGoogle Scholar
  28. 28.
    Prather AA, Janicki-Deverts D, Hall MH, Cohen S (2015) Behaviorally assessed sleep and susceptibility to the common cold. Sleep 38(9):1353–1359.  https://doi.org/10.5665/sleep.4968 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Prather AA, Leung CW (2016) Association of insufficient sleep with respiratory infection among adults in the United States. JAMA Intern Med 176(6):850–852.  https://doi.org/10.1001/jamainternmed.2016.0787 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Said EA, Dupuy FP, Trautmann L, Zhang YW, Shi Y, El-Far M, Hill BJ, Noto A, Ancuta P, Peretz Y, Fonseca SG, Van Grevenynghe J, Boulassel MR, Bruneau J, Shoukry NH, Routy JP, Douek DC, Haddad EK, Sekaly RP (2010) Programmed death-1-induced interleukin-10 production by monocytes impairs CD4(+) T cell activation during HIV infection. Nat Med 16(4):452–U136.  https://doi.org/10.1038/nm.2106 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Lange T, Perras B, Fehm HL, Born J (2003) Sleep enhances the human antibody response to hepatitis A vaccination. Psychosom Med 65(5):831–835.  https://doi.org/10.1097/01.Psy.0000091382.61178.F1 CrossRefPubMedGoogle Scholar
  32. 32.
    Spiegel K, Sheridan JF, Van Cauter E (2002) Effect of sleep deprivation on response to immunizaton. JAMA 288(12):1471–1472.  https://doi.org/10.1001/jama.288.12.1471-a CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Elias A. Said
    • 1
    Email author
  • Mohammed A. Al-Abri
    • 2
  • Iman Al-Saidi
    • 1
  • Mohammed S. Al-Balushi
    • 1
  • Jumaa Z. Al-Busaidi
    • 1
  • Iman Al-Reesi
    • 1
  • Crystal Y. Koh
    • 1
  • Mohamed A. Idris
    • 1
  • Ali A. Al-Jabri
    • 1
  • Omar Habbal
    • 3
  1. 1.Department of Microbiology and Immunology, College of Medicine and Health SciencesSultan Qaboos UniversityMuscatOman
  2. 2.Department of Clinical PhysiologySultan Qaboos University HospitalMuscatOman
  3. 3.Department of Human & Clinical Anatomy, College of Medicine and Health SciencesSultan Qaboos UniversityMuscatOman

Personalised recommendations