Skip to main content
SpringerLink
Log in

Sleep Disturbances Increase Interleukin-6 Production During Pregnancy: Implications for Pregnancy Complications

  • Original Articles
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Pregnant women experience disturbed sleep that varies throughout the gestational period. In clinical studies of nonpregnant cohorts, data link disturbed sleep with increases in inflammatory markers. Emerging evidence has also found associations between increased inflammation and medical morbidity, including various pregnancy complications. The authors have previously shown a correlation between sleep disturbances and serum cytokine levels. They extend this initial observation by evaluating the relationship between sleep during mid and late pregnancy and inflammatory cytokines in both serum and stimulated peripheral blood mononuclear cells. Subjective sleep during pregnancy, described by the Pittsburgh Sleep Quality Index and sleep diaries, and circulating and stimulated measures of interleukin (IL)—6 and tumor necrosis factor (TNF)— α were evaluated in 19 pregnant women. The authors found that greater sleep complaints in late pregnancy were associated with both increased circulating and stimulated IL-6 levels. Short sleep duration and poor sleep efficiency in both mid and late pregnancy were associated with higher stimulated levels of IL-6. No relationships were observed for TNF- α. These preliminary findings indicate that women who experience sleep disturbances as early as mid gestation are likely to have an increase in inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hertz G., Fast A., Feinsilver SH, Albertario CL, Schulman H., Fein AM Sleep in normal late pregnancy. Sleep. 1992;15(3): 246–251.

    Article  CAS  PubMed  Google Scholar 

  2. Lee KA, Zaffke ME, McEnany G. Parity and sleep patterns during and after pregnancy. Obstet Gynecol. 2000;95(1):14–18.

    CAS  PubMed  Google Scholar 

  3. Mindell JA, Jacobson BJ Sleep disturbances during pregnancy. J Obstet Gynecol Neonatal Nurs. 2000;29(6):590–597.

    Article  CAS  PubMed  Google Scholar 

  4. Okun ML, Coussons-Read ME Sleep disruption during pregnancy: how does it influence serum cytokines? J Reprod Immunol. 2007;73(2):158–165.

    Article  CAS  PubMed  Google Scholar 

  5. Breslau N., Roth T., Rosenthal L., Andreski P. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39(6):411–418.

    Article  CAS  PubMed  Google Scholar 

  6. Ford DE, Cooper-Patrick L. Sleep disturbances and mood disorders: an epidemiologic perspective. Depress Anxiety. 2001; 14(1):3–6.

    Article  CAS  PubMed  Google Scholar 

  7. Perlis ML, Giles DE, Buysse DJ, Tu X., Kupfer DJ Self-reported sleep disturbance as a prodromal symptom in recurrent depression. J Affect Disord. 1997;42(2–3):209–212.

    Article  CAS  PubMed  Google Scholar 

  8. Jennings JR, Muldoon MF, Hall M., Buysse DJ, Manuck SB Self-reported sleep quality is associated with the metabolic syndrome. Sleep. 2007;30(2):219–223.

    Article  PubMed  Google Scholar 

  9. Knutson KL, Ryden AM, Mander BA, Van Cauter E. Role of sleep duration and quality in the risk and severity of type 2 diabetes mellitus. Arch Intern Med. 2006;166(16): 1768–1774.

    Article  PubMed  Google Scholar 

  10. Meisinger C., Heier M., Loewel H. Sleep disturbance as a predictor of type 2 diabetes mellitus in men and women from the general population. Diabetologia. 2005;48(2):235–241.

    Article  CAS  PubMed  Google Scholar 

  11. Punjabi NM, Ahmed MM, Polotsky VY, Beamer BA, O’Donnell CP Sleep-disordered breathing, glucose intolerance, and insulin resistance. Respir Physiol Neurobiol. 2003;136(2–3): 167–178.

    Article  CAS  PubMed  Google Scholar 

  12. Spiegel K., Knutson K., Leproult R., Tasali E., Van Cauter E. Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes. J Appl Physiol. 2005;99(5):2008–2019.

    Article  CAS  PubMed  Google Scholar 

  13. Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab. 2000;85(3):1151–1158.

    Article  CAS  PubMed  Google Scholar 

  14. Dimitrov S., Lange T., Tieken S., Fehm HL, Born J. Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans. Brain Behav Immun. 2004;18(4):341–348.

    Article  CAS  PubMed  Google Scholar 

  15. Irwin MR, Wang M., Campomayor CO, Collado-Hidalgo A., Cole S. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med. 2006;166(16):1756–1762.

    Article  CAS  PubMed  Google Scholar 

  16. Redwine L., Hauger RL, Gillin JC, Irwin M. Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans. J Clin Endocrinol Metab. 2000;85(10):3597–3603.

    CAS  PubMed  Google Scholar 

  17. von Kanel R., Dimsdale JE, Ancoli-Israel S., et al. Poor sleep is associated with higher plasma proinflammatory cytokine interleukin-6 and procoagulant marker fibrin D-dimer in older caregivers of people with Alzheimer’s disease. J Am Geriatr Soc. 2006;54(3):431–437.

    Article  Google Scholar 

  18. Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Circadian interleukin-6 secretion and quantity and depth of sleep. J Clin Endocrinol Metab. 1999;84(8):2603–2607.

    Article  CAS  PubMed  Google Scholar 

  19. Himmerich H., Beitinger PA, Fulda S., et al. Plasma levels of tumor necrosis factor alpha and soluble tumor necrosis factor receptors in patients with narcolepsy. Arch Intern Med. 2006;166(16):1739–1743.

    Article  CAS  PubMed  Google Scholar 

  20. Vgontzas AN, Zoumakis E., Bixler EO, et al. Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. J Clin Endocrinol Metab. 2004;89(5): 2119–2126.

    Article  CAS  PubMed  Google Scholar 

  21. Qiu C., Sorensen TK, Luthy DA, Williams MA A prospective study of maternal serum C-reactive protein (CRP) concentrations and risk of gestational diabetes mellitus. Paediatr Perinat Epidemiol. 2004;18(5):377–384.

    Article  PubMed  Google Scholar 

  22. Romero R., Espinoza J., Goncalves LF, Kusanovic JP, Friel LA, Nien JK Inflammation in preterm and term labour and delivery. Semin Fetal Neonatal Med. 2006;11(5): 317–326.

    Google Scholar 

  23. Dinarello CA Proinflammatory cytokines. Chest. 2000;118(2): 503–508.

    Article  CAS  PubMed  Google Scholar 

  24. Afshari JT, Ghomian N., Shameli A., et al. Determination of interleukin-6 and tumor necrosis factor-alpha concentrations in Iranian-Khorasanian patients with preeclampsia. BMC Pregnancy Childbirth. 2005;5:14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Ategbo JM, Grissa O., Yessoufou A., et al. Modulation of adipokines and cytokines in gestational diabetes and macrosomia. J Clin Endocrinol Metab. 2006;91(10):4137–4143.

    Article  CAS  PubMed  Google Scholar 

  26. Bartha JL, Romero-Carmona R., Comino-Delgado R. Inflammatory cytokines in intrauterine growth retardation. Acta Obstet Gynecol Scand. 2003;82(12):1099–1102.

    Article  PubMed  Google Scholar 

  27. Backhaus J., Jughanns K., Broocks A., Riemann D., Hohagen F. Test-retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia. J Psychosom Res. 2002; 53(3):737–740.

    Article  PubMed  Google Scholar 

  28. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28: 193–213.

    CAS  PubMed  Google Scholar 

  29. Carpenter JS, Andrykowski MA Psychometric evaluation of the Pittsburgh Sleep Quality Index. J Psychosom Res. 1998; 45(1 Spec No):5–13.

    Article  CAS  PubMed  Google Scholar 

  30. Quan SF, Howard BV, Iber C., et al. The Sleep Heart Health Study: design, rationale, and methods. Sleep. 1997;20(12): 1077–1085.

    CAS  PubMed  Google Scholar 

  31. Tishler PV, Larkin EK, Schluchter MD, Redline S. Incidence of sleep-disordered breathing in an urban adult population: the relative importance of risk factors in the development of sleep-disordered breathing. JAMA. 2003;289(17):2230–2237.

    Article  PubMed  Google Scholar 

  32. Young T., Peppard PE, Gottlieb DJ Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165(9):1217–1239.

    Article  PubMed  Google Scholar 

  33. Walsleben JA, Kapur VK, Newman AB, et al. Sleep and reported daytime sleepiness in normal subjects: the Sleep Heart Health Study. Sleep. 2004;27(2):293–298.

    Article  PubMed  Google Scholar 

  34. Lichstein KL, Durrence HH, Taylor DJ, Bush AJ, Riefel BW Quantitative criteria for insomnia. Behav Res Ther. 2003;41(4): 427–445.

    Article  CAS  PubMed  Google Scholar 

  35. Pien GW, Schwab RJ Sleep disorders during pregnancy. Sleep. 2004;27(7):1405–1417.

    Article  PubMed  Google Scholar 

  36. Redwine L., Dang J., Hall M., Irwin M. Disordered sleep, nocturnal cytokines, and immunity in alcoholics. Psychosom Med. 2003;65(1):75–85.

    Article  CAS  PubMed  Google Scholar 

  37. Vgontzas AN, Bixler EO, Lin HM, Prolo P., Trakada G., Chrousos GP IL-6 and its circadian secretion in humans. Neuroimmunomodulation. 2005;12(3):131–140.

    Article  CAS  PubMed  Google Scholar 

  38. Hogan D., Morrow JD, Smith EM, Opp MR Interleukin-6 alters sleep of rats. J Neuroimmunol. 2003;137(1–2):59–66.

    Article  CAS  PubMed  Google Scholar 

  39. Krueger JM, Fang J., Taishi P., Chen Z., Kushikata T., Gardi J. Sleep: a physiologic role for IL-1 beta and TNF-alpha. Ann N Y Acad Sci. 1998;856:148–159.

    Article  CAS  PubMed  Google Scholar 

  40. Everson CA Clinical assessment of blood leukocytes, serum cytokines, and serum immunoglobulins as responses to sleep deprivation in laboratory rats. Am J Physiol Reg Integr Comp Physiol. 2005;289(4):R1054–R1063.

    CAS  Google Scholar 

  41. Opp M., Born J., Irwin M. Sleep and the immune system. In: Ader R, ed. Psychoneuroimmunology. 4th ed. New York:Academic Press;2006:539–578.

    Google Scholar 

  42. Okun ML, Giese S., Lin L., Einen M., Mignot E., Coussons-Read ME Exploring the cytokine and endocrine involvement in narcolepsy. Brain Behav Immun. 2004;18(4):326–332.

    Article  CAS  PubMed  Google Scholar 

  43. Vgontzas AN, Papanicolaou DA, Bixler EO, Kales A., Tyson K., Chrousos GP Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab. 1997;82(5):1313–1316.

    Article  CAS  PubMed  Google Scholar 

  44. Friedman EM, Hayney MS, Love GD, et al. Social relationships, sleep quality, and interleukin-6 in aging women. Proc Natl Acad Sci U S A. 2005;102(51):18757–18762.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Salas-Salvado J., Bullo M., Garcia-Lorda P., et al. Subcutaneous adipose tissue cytokine production is not responsible for the restoration of systemic inflammation markers during weight loss. Int J Obes (Lond). 2006;30(12):1714–1720.

    Article  CAS  Google Scholar 

  46. Stotland NE, Haas JS, Brawarsky P., Jackson RA, Fuentes-Afflick E., Escobar GJ Body mass index, provider advice, and target gestational weight gain. Obstet Gynecol. 2005;105(3): 633–638.

    Article  PubMed  Google Scholar 

  47. Ciftci TU, Kokturk O., Bukan N., Bilgihan A. The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome. Cytokine. 2004;28(2):87–91.

    Article  CAS  PubMed  Google Scholar 

  48. Arntzen KJ, Kjollesdal AM, Halgunset J., Vatten L., Austgulen R. TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor. J Perinat Med. 1998; 26(1):17–26.

    Article  CAS  PubMed  Google Scholar 

  49. Azizieh F., Raghupathy R., Makhseed M. Maternal cytokine production patterns in women with pre-eclampsia. Am J Reprod Immunol. 2005;54(1):30–37.

    Article  CAS  PubMed  Google Scholar 

  50. Edwards N., Blyton CM, Kesby GJ, Wilcox I., Sullivan CE Pre-eclampsia is associated with marked alterations in sleep architecture. Sleep. 2000;23(5):619–625.

    Article  CAS  PubMed  Google Scholar 

  51. Ekholm EM, Polo O., Rauhala ER, Ekblad UU Sleep quality in preeclampsia. Am J Obstet Gynecol. 1992;167(5):1262–1266.

    Article  CAS  PubMed  Google Scholar 

  52. Lee KA, Gay CL Sleep in late pregnancy predicts length of labor and type of delivery. Am J Obstet Gynecol. 2004;191(6): 2041–2046.

    Article  PubMed  Google Scholar 

  53. Kimura M., Zhang SQ, Inoue S. Pregnancy-associated sleep changes in the rat. Am J Physiol. 1996;271(4 pt 2):R1063–R1069.

    CAS  PubMed  Google Scholar 

  54. Krueger JM, Obal F. Jr, Fang J., Kubota T., Taishi P. The role of cytokines in physiological sleep regulation. Ann N Y Acad Sci. 2001;933(1):211–221.

    Article  CAS  PubMed  Google Scholar 

  55. Opp MR Cytokines and sleep. Sleep Med Rev. 2005;9(5): 355–364.

    Article  PubMed  Google Scholar 

  56. Frey DJ, Fleshner M., Wright KP Jr. The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults. Brain Behav Immun. Epub ahead of print May 22, 2007.

  57. Irwin M. Effects of sleep and sleep loss on immunity and cytokines. Brain Behav Immun. 2002;16(5):503–512.

    Article  CAS  PubMed  Google Scholar 

  58. Irwin M., McClintick J., Costlow C., Fortner M., White J., Gillin JC Partial night sleep deprivation reduces natural killer and cellular immune responses in humans. FASEB J. 1996;10(5): 643–653.

    Article  CAS  PubMed  Google Scholar 

  59. Shearer WT, Reuben JM, Mullington JM, et al. Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight. J Allergy Clin Immunol. 2001;107(1):165–170.

    Article  CAS  PubMed  Google Scholar 

  60. Conrad KP, Miles TM, Benyo DF Circulating levels of immunoreactive cytokines in women with preeclampsia. Am J Reprod Immunol. 1998;40(2):102–111.

    Article  CAS  PubMed  Google Scholar 

  61. Luppi P., DeLoia JA Monocytes of preeclamptic women spontaneously synthesize pro-inflammatory cytokines. Clin Immunol. 2006;118(2–3):268–275.

    Article  CAS  PubMed  Google Scholar 

  62. Munno I., Chiechi LM, Lacedra G., et al. Spontaneous and induced release of prostaglandins, interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha by placental tissue from normal and preeclamptic pregnancies. Am J Reprod Immunol. 1999;42(6):369–374.

    Article  CAS  PubMed  Google Scholar 

  63. Meier-Ewert HK, Ridker PM, Rifai N., Price N., Dinges DF, Mullington JM Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem. 2001;47(3):426–430.

    CAS  PubMed  Google Scholar 

  64. Maasilta P., Bachour A., Teramo K., Polo O., Laitinen LA Sleep-related disordered breathing during pregnancy in obese women. Chest. 2001;120(5):1448–1454.

    Article  CAS  PubMed  Google Scholar 

  65. Guilleminault C., Kirisoglu C., Ohayon MM C-reactive protein and sleep-disordered breathing. Sleep. 2004;27(8): 1507–1511.

    Article  PubMed  Google Scholar 

  66. Yao M., Tachibana N., Okura M., et al. The relationship between sleep-disordered breathing and high-sensitivity C-reactive protein in Japanese men. Sleep. 2006;29(5):661–665.

    PubMed  Google Scholar 

  67. Yinon D., Lowenstein L., Suraya S., et al. Pre-eclampsia is associated with sleep-disordered breathing and endothelial dysfunction. Eur Respir J. 2006;27(2):328–333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Roberts JM Pregnancy-related hypertension. In: Creasey RK, Resnik R, eds. Maternal-Fetal Medicine. Philadelphia, PA:Saunders;2004:859–899.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Pittsburgh Medical Center/Western Psychiatric Institute & Clinic, Pittsburgh, Pennsylvania, USA

    Michele L. Okun PhD & Martica Hall PhD

  2. University of Colorado at Denver and Health Sciences Center, CB 173, PO Box 173364, Denver, CO, 80217-3364, USA

    Michele L. Okun PhD & Mary E. Coussons-Read PhD

Authors
  1. Michele L. Okun PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martica Hall PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mary E. Coussons-Read PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mary E. Coussons-Read PhD.

Additional information

Work was conducted at the University of Colorado Denver and Health Sciences Center and was supported by a Clinical Training Grant in Psychiatry (MH016804).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Okun, M.L., Hall, M. & Coussons-Read, M.E. Sleep Disturbances Increase Interleukin-6 Production During Pregnancy: Implications for Pregnancy Complications. Reprod. Sci. 14, 560–567 (2007). https://doi.org/10.1177/1933719107307647

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719107307647

Key words

Search

Navigation