Skip to main content
Log in

The Association of Circulatory Cytokines (IL-6 and IL-10) Level with Spontaneous Abortion—a Preliminary Observation

  • Reproductive Biology: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Successful pregnancy or its outcome depends upon various endogenous and exogenous determinants including immune status, and cytokines are one of the regulators which might play a vital role in the maintenance of pregnancy. The study was carried out to determine the role of cytokines, i.e., interleukin-6 (IL-6) and interleukin-10 (IL-10), in spontaneous abortion (SAb) cases with reference to control (women without SAb). One hundred twenty-six subjects (63 women with SAb cases and 63 control women without SAb and bearing at least one child) were enrolled. Out of the 63 SAb cases, 31 women from Outpatient Department (with history of SAb cases, i.e., one, two, or more) and 32 from the Gynecology ward (current SAb cases) were enrolled. The cytokines (IL-6 and IL-10) were measured by ELISA method using commercially available kit. The mean IL-6 level was higher among women with SAb cases, recent SAb and recurrent SAb cases versus controls, history of SAb and less than 2 SAb cases respectively, while an inverse pattern of variations was observed for IL-10 level. The Spearman’s correlation revealed that the IL-6 was positively correlated while IL-10 was negatively correlated with number of incidences of SAbs. The data of women with recent SAb and childbirth were categorized into four IL quartiles and found that the highest % of control and lowest % of SAb subjects were in second quartile of IL-6 while highest % of control and lowest % of SAb subjects were in the fourth (high) quartile of IL-10 level group. A multiple regression model showed that with elevation in IL-6, there was an elevation in number of SAb cases and an inverse relationship was observed with regard to IL-10. The results indicate positive role of IL-10 and undesirable role of IL-6 on pregnancy outcomes. Further, quartiles’ distribution suggests that high levels of IL-10 might be necessary for the effective pregnancy outcome, but more data are needed to substantiate the present findings.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

IL-6:

interleukin-6

IL-10:

interleukin-10

SAb:

spontaneous abortion

Pg:

picogram

ml:

milliliter

n:

number

yr:

year

kg:

kilogram

m2 :

meter squared

%:

percentage

Q1:

quartile first

Q2:

quartile second

Q3:

quartile third

Q4:

quartile Fourth

CRP:

C-reactive protein

URSA:

unexplained recurrent spontaneous abortion

BMI:

body mass index

RSA/ RSAb:

recurrent spontaneous abortion

MDA:

malondialdehyde

ELISA:

enzyme-linked immunosorbent assay

References

  1. Seyhon I, Mohammadi P, Kaki A, Mazdapour M. Evaluation of endothelial nitric oxide synthase gene G894T polymorphism in Iranian women with recurrent spontaneous abortions. Indian J Fundam Appl Life Sci. 2014;4(S3):1194–8.

    Google Scholar 

  2. Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009;2(2):76–83.

    PubMed  PubMed Central  Google Scholar 

  3. Morelli SS, Mandal M, Goldsmith LT, Kashani BN, Nicholas PNM. The maternal immune system during pregnancy and its influence on fetal development. Res Report Biol. 2015;6:171–89.

    Article  CAS  Google Scholar 

  4. Mobini M, Mortazavi M, Nadi S, Zare-Bidaki M, Pourtalebi S, Arababadi MK. Significant roles played by interleukin-10 in outcome of pregnancy. Iran J Basic Med Sci. 2016;19(2):119–24.

    PubMed  PubMed Central  Google Scholar 

  5. Prins JR, Gomez-Lopez N, Robertson SA. Interleukin-6 in pregnancy and gestational disorders. J Reprod Immunol. 2012;95(1–2):1–4.

    Article  CAS  Google Scholar 

  6. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295. https://doi.org/10.1101/cshperspect.a016295.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Saraiva M, O'garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010;10(3):170–81. https://doi.org/10.1038/nri2711.

    Article  CAS  PubMed  Google Scholar 

  8. McGeough MD, Pena CA, Mueller JL, Pociask DA, Broderick L, Hoffman HM, et al. Cutting edge: IL-6 is a marker of inflammation with no direct role in inflammasome-mediated mouse models. J Immunol. 2012;189(6):2707–11. https://doi.org/10.4049/jimmunol.1101737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mor G, Cardenas I, Abrahams V, Guller S. Inflammation, and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci. 2011;1221(1):80–7.

    Article  CAS  Google Scholar 

  10. Mallmann P, Mallmann R, Krebs D. Determination of tumor necrosis factor alpha (TNFα) and interleukin 2 (IL2) in women with idiopathic recurrent miscarriage. Arch Gynecol Obstet. 1991;249(2):73–8.

    Article  CAS  Google Scholar 

  11. Chatterjee P, Chiasson VL, Bounds KR, Mitchell BM. Regulation of the anti-inflammatory cytokine’s interleukin-4 and interleukin-10 during pregnancy. Front Immunol. 2014;5:253. https://doi.org/10.3389/fimmu.2014.00253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cai J, Li M, Huang Q, Fu X, Wu H. Differences in cytokine expression and STAT3 activation between healthy controls and patients of unexplained recurrent spontaneous abortion (URSA) during early pregnancy. PloS One. 2016;11(9):e0163252.

    Article  Google Scholar 

  13. Wei SQ, Fraser W, Luo ZC. Inflammatory cytokines and spontaneous preterm birth in asymptomatic women: a systematic review. Obstet Gynecol. 2010;116:393–401.

    Article  Google Scholar 

  14. Abdulkhaliq RJ, Mohammed S, Abbas AH. The role of IL-6 and TGF-β1 in Iraqi women with recurrent abortion. J Global Pharma Technol. 2018;10(03):633–9.

    Google Scholar 

  15. Drozdzik M, Szlarb N, Kurzawski M. Interleukin-6 level and gene polymorphism in spontaneous miscarriage. Tissue Antigens. 2013;82(3):171–6.

    Article  CAS  Google Scholar 

  16. Galazios G, Tsoulou S, Zografou C, Tripsianis G, Koutlaki N, Papazoglou D, et al. The role of cytokines IL-6 and IL-8 in the pathogenesis of spontaneous abortions. J Matern Fetal Neonatal Med. 2011;24(10):1283–5.

    Article  CAS  Google Scholar 

  17. Bohiltea CL, Radoi VE. Interleukin-6 and interleukin-10 gene polymorphisms and recurrent pregnancy loss in Romanian population. Iranian J Reprod Med. 2014;12(9):617–22.

    Google Scholar 

  18. Su D, Zhang Y, Wang Q, Wang J, Jiao B, Wang G, et al. Association of interleukin-10 gene promoter polymorphisms with recurrent miscarriage: a meta-analysis. Am J Reprod Immunol. 2016;76(2):172–80.

    Article  CAS  Google Scholar 

  19. Cheng SB, Sharma S. Interleukin-10: a pleiotropic regulator in pregnancy. Am J Reprod Immunol. 2015;73(6):487–500.

    Article  CAS  Google Scholar 

  20. Piccinni MP, Giudizi MG, Biagiotti R, Beloni L, Giannarini L, Sampognaro S, et al. Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones. J Immunol. 1995;155(1):128–33.

    CAS  PubMed  Google Scholar 

  21. Hudic I, Fatusic Z. Progesterone-induced blocking factor (PIBF) and Th (1)/Th (2) cytokine in women with threatened spontaneous abortion. J Perinat Med. 2009;37(4):338–42.

    Article  CAS  Google Scholar 

  22. Houra M, Nazem-Kazerani F, Mortazavi M, Hadavi M, Moosavi SM, Arababadi MK. The roles played by IL-10, IL-23 and IL-17A in term delivery. J Neonatal-Perinatal Med. 2020;1–9. https://doi.org/10.3233/NPM-190360.

  23. Azizieh FY, Raghupathy RR. IL-10 and pregnancy complications. Clin Exptl Obstet Gynecol. 2017;44(2):252–8. https://doi.org/10.12891/ceog3456.2017.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are thankful to the participants for cooperation. The authors are also thankful to NIOH for providing the initial intramural support to the study.

Funding

Initial intramural support from NIOH and later RT received Senior Research Fellowship from ICMR.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sunil Kumar.

Ethics declarations

An ethical approval of the study was acquired from the institutional ethical committee of National Institute of Occupational Health, Ahmedabad, India. An informed consent was attained from each participant, after explaining the objectives as well as benefits of the study, at the time of questionnaire interview of the participants.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Thaker, R., Oza, H., Verma, V. et al. The Association of Circulatory Cytokines (IL-6 and IL-10) Level with Spontaneous Abortion—a Preliminary Observation. Reprod. Sci. 28, 857–864 (2021). https://doi.org/10.1007/s43032-020-00292-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-020-00292-6

Keywords

Navigation