Association of circulating IL-6 and IL-10 levels during mid-gestation with recurrent pregnancy loss history and severity: a South Indian study

Sufaya Jameel , Rashmi Bhuwalka , Parveen Jahan

Exploration of Immunology ›› 2025, Vol. 5 ›› Issue (1) : 1003209

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Exploration of Immunology ›› 2025, Vol. 5 ›› Issue (1) :1003209 DOI: 10.37349/ei.2025.1003209
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Association of circulating IL-6 and IL-10 levels during mid-gestation with recurrent pregnancy loss history and severity: a South Indian study
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Abstract

Aim:Recurrent pregnancy loss (RPL) is defined as the loss of two or more clinical pregnancies before the 20th week of gestation. Globally, RPL affects 1–5% of couples, with approximately 50% of cases remaining idiopathic. This study aimed to assess the circulating levels of interleukin-6 (IL-6) and IL-10 cytokines in pregnant women with and without a history of RPL.

Methods:A total of 170 pregnant women in their second trimester with and without a history of RPL were enrolled from Niloufer Hospital, South India. Serum samples isolated from blood were analyzed using a sandwich-enzyme linked immunosorbent assay (ELISA) to estimate IL-6 and IL-10 levels.

Results:The median age was significantly higher in the RPL group (25 years) compared to the non-RPL (NRPL) group (22 years) (p = 0.0001). Similarly, body mass index (BMI) was significantly elevated in the RPL group (25.64 kg/m2) vs. the NRPL group (22.51 kg/m2) (p = 0.0001). The analysis revealed significantly elevated IL-6 and reduced IL-10 levels in the RPL group compared to the NRPL group (p = 0.0001). Additionally, the IL-6/IL-10 ratio differed significantly between the two groups. Receiver operating characteristic (ROC) curve analysis indicated that IL-6 was a better marker for RPL than IL-6/IL-10 ratio and IL-10. IL-10 levels were found to be a reliable marker in relation to the extent of pregnancy loss history.

Conclusions:The study highlights the presence of a pro-inflammatory systemic milieu in mid-gestation among women with a history of RPL, potentially reflecting the immunological environment at the feto-placental interface. Further research to establish a distinct cytokine signature between RPL and NRPL groups may facilitate the development of targeted preventive and therapeutic strategies. However, the current findings are limited by a modest sample size and a homogenous ethnic population, which may affect generalizability. Larger, multi-ethnic studies are warranted to validate these observations and enhance clinical applicability.

Keywords

Recurrent pregnancy loss (RPL) / non-RPL (NRPL) / interleukin-6 (IL-6) / IL-10 / receiver operating characteristic (ROC)

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Sufaya Jameel, Rashmi Bhuwalka, Parveen Jahan. Association of circulating IL-6 and IL-10 levels during mid-gestation with recurrent pregnancy loss history and severity: a South Indian study. Exploration of Immunology, 2025, 5 (1) : 1003209 DOI:10.37349/ei.2025.1003209

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References

[1]

Madduru D, Supriya K, Dirsipam K. Relation between MTHFR (Methylenetetrahydrofolate Reductase) gene functional polymorphisms and magnitude of Recurrent Pregnancy Losses (RPL) among women with low socio-economic status in Asian Indians. Genet Mol Res. 2019; 18.

[2]

Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012; 98: 1103-11.

[3]

Stephenson MD. Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril. 1996; 66: 24-9.

[4]

Imam SN, Shamsi MB, Kumar K, Deka D, Dada R. Idiopathic recurrent pregnancy loss: role of paternal factors; a pilot study. J Reprod Infertil. 2011; 12: 267-76.

[5]

Jameel S, Bhuwalka R, Begum M, Bonu R, Jahan P. Circulating levels of cytokines (IL-6, IL-10 and TGF-β) and CD4+CD25+FOXP3+Treg cell population in recurrent pregnancy loss . Reprod Biol. 2024; 24: 100842.

[6]

Rashid N, Nigam A, Saxena P, Jain SK, Wajid S. Association of IL-1β, IL-1Ra and FABP1 gene polymorphisms with the metabolic features of polycystic ovary syndrome. Inflamm Res. 2017; 66: 621-36.

[7]

Saini V, Arora S, Yadav A, Bhattacharjee J. Cytokines in recurrent pregnancy loss. Clin Chim Acta. 2011; 412: 702-8.

[8]

Dutta S, Sengupta P. Defining pregnancy phases with cytokine shift. J Pregnancy Reprod. 2017; 1: 1-3.

[9]

Mor G, Koga K. Macrophages and Pregnancy. Reprod Sci. 2008; 15: 435-6.

[10]

Daher S, de Arruda Geraldes Denardi K, Blotta MH, Mamoni RL, Reck AP, Camano L, et al. Cytokines in recurrent pregnancy loss. J Reprod Immunol. 2004; 62: 151-7.

[11]

Silver RM, Branch DW, Goldenberg R, Iams JD, Klebanoff MA. Nomenclature for pregnancy outcomes: time for a change. Obstet Gynecol. 2011; 118: 1402-8.

[12]

El Hachem H, Crepaux V, May-Panloup P, Descamps P, Legendre G, Bouet PE. Recurrent pregnancy loss: current perspectives. Int J Womens Health. 2017; 9: 331-45.

[13]

Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells . Nature. 2006; 441: 235-8.

[14]

Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, et al. Transforming growth factor-β induces development of the TH17 lineage . Nature. 2006; 441: 231-4.

[15]

Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGFβ in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells. Immunity. 2006; 24: 179-89.

[16]

Fantini MC, Becker C, Monteleone G, Pallone F, Galle PR, Neurath MF. Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7 . J Immunol. 2004; 172: 5149-53.

[17]

Dominitzki S, Fantini MC, Neufert C, Nikolaev A, Galle PR, Scheller J, et al. Cutting edge: trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+CD25 T cells . J Immunol. 2007; 179: 2041-5.

[18]

Fujimoto VY, Kim D, vom Saal FS, Lamb JD, Taylor JA, Bloom MS. Serum unconjugated bisphenol A concentrations in women may adversely influence oocyte quality during in vitro fertilization. Fertil Steril. 2011; 95: 1816-9.

[19]

Atreya R, Mudter J, Finotto S, Müllberg J, Jostock T, Wirtz S, et al. Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: Evidence in Crohn disease and experimental colitis in vivo . Nat Med. 2000; 6: 583-8.

[20]

Yoshida H, Hashizume M, Suzuki M, Mihara M. Anti-IL-6 receptor antibody suppressed T cell activation by inhibiting IL-2 production and inducing regulatory T cells. Eur J Pharmacol. 2010; 634: 178-83.

[21]

Rincón M, Anguita J, Nakamura T, Fikrig E, Flavell RA. Interleukin (IL)-6 Directs the Differentiation of IL-4-producing CD4+ T Cells . J Exp Med. 1997; 185: 461-9.

[22]

Banerjee M, Saxena M. Interleukin-1 (IL-1) family of cytokines: Role in Type 2 Diabetes. Clin Chim Acta. 2012; 413: 1163-70.

[23]

Tanaka T, Narazaki M, Kishimoto T. IL-6 in Inflammation, Immunity, and Disease. Cold Spring Harb Perspect Biol. 2014; 6: a016295.

[24]

Gabay C. Interleukin-6 and chronic inflammation. Arthritis Res Ther. 2006; 8 Suppl 2: S3.

[25]

Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol. 2021; 33: 127-48.

[26]

Cheng SB, Sharma S. Interleukin-10: A Pleiotropic Regulator in Pregnancy. Am J Reprod Immunol. 2015; 73: 487-500.

[27]

Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 2008; 226: 205-18.

[28]

Thaxton JE, Sharma S. Interleukin-10: A Multi-Faceted Agent of Pregnancy. Am J Reprod Immunol. 2010; 63: 482-91.

[29]

Hennessy S, Bilker WB, Berlin JA, Strom BL. Factors influencing the optimal control-to-case ratio in matched case-control studies. Am J Epidemiol. 1999; 149: 195-7.

[30]

Raghupathy R, Khan SF, Syamasundar PV, Bansal P, Azizieh F. A Placenta-Derived Suppressor Factor with a T-Cell Bias. Am J Reprod Immunol. 1999; 42: 205-18.

[31]

Plevyak M, Hanna N, Mayer S, Murphy S, Pinar H, Fast L, et al. Deficiency of Decidual IL-10 in First Trimester Missed Abortion: A Lack of Correlation with the Decidual Immune Cell Profile. Am J Reprod Immunol. 2002; 47: 242-50.

[32]

Banerjee P, Ghosh S, Dutta M, Subramani E, Khalpada J, Roychoudhury S, et al. Identification of Key Contributory Factors Responsible for Vascular Dysfunction in Idiopathic Recurrent Spontaneous Miscarriage. PLoS One. 2013; 8: e80940.

[33]

Wang X, Wong K, Ouyang W, Rutz S. Targeting IL-10 Family Cytokines for the Treatment of Human Diseases. Cold Spring Harb Perspect Biol. 2019; 11: a028548.

[34]

Calleja-Agius J, Brincat MP. Recurrent miscarriages: What is the role of cytokines? Gynaecological Endocrinology. 2008; 24: 663-8.

[35]

Vilotić A, Nacka-Aleksić M, Pirković A, Bojić-Trbojević Ž, Dekanski D, Krivokuća MJ. IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies. Int J Mol Sci. 2022; 23: 14574.

[36]

Magnus MC, Wilcox AJ, Morken N, Weinberg CR, Håberg SE. Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study. BMJ. 2019; 364: l869.

[37]

Eapen A, Hayes ET, McQueen DB, Beestrum M, Eyck PT, Boots C. Mean differences in maternal body mass index and recurrent pregnancy loss: a systematic review and meta-analysis of observational studies. Fertil Steril. 2021; 116: 1341-8.

[38]

Ng KYB, Cherian G, Kermack AJ, Bailey S, Macklon N, Sunkara SK, et al. Systematic review and meta-analysis of female lifestyle factors and risk of recurrent pregnancy loss. Sci Rep. 2021; 11: 7081.

[39]

Cavalcante MB, Sarno M, Peixoto AB, Júnior E, Barini R. Obesity and recurrent miscarriage: A systematic review and meta-analysis. J Obstet Gynaecol Res. 2019; 45: 30-8.

[40]

Pandey M, Chauhan M, Awasthi S. Interplay of cytokines in preterm birth. Indian J Med Res. 2017; 146: 316-27.

[41]

Tyagi P, Alharthi NS. Evaluation of Pro-inflammatory Cytokine Level in Cases of Idiopathic Recurrent Spontaneous Miscarriage in Saudi Arabia. Biomed Biotechnol Res J. 2020; 4: 225-31.

[42]

Ma J, Zhang X, He G, Yang C. Association between TNF, IL1B, IL6, IL10 and IFNG polymorphisms and recurrent miscarriage: a case control study . Reprod Biol Endocrinol. 2017; 15: 83.

[43]

Prins JR, Gomez-Lopez N, Robertson SA. Interleukin-6 in pregnancy and gestational disorders. J Reprod Immunol. 2012; 95: 1-14.

[44]

Bates MD, Quenby S, Takakuwa K, Johnson PM, Vince GS. Aberrant cytokine production by peripheral blood mononuclear cells in recurrent pregnancy loss? Hum Reprod. 2002; 17: 2439-44.

[45]

Abdullah GA, Mahdi K. The Role of Cytokines among Women with Spontaneous Miscarriage. Med J Islam World Acad Sci. 2013; 21: 119-24.

[46]

Bahadori M, Zarei S, Zarnani AH, Zarei O, Idali F, Hadavi R, et al. IL-6, IL-10 and IL-17 gene polymorphisms in Iranian women with recurrent miscarriage. Iran J Immunol. 2014; 11: 97-104.

[47]

Parveen F, Shukla A, Agarwal S. Cytokine gene polymorphisms in northern Indian women with recurrent miscarriages. Fertil Steril. 2013; 99: 433-40.

[48]

Fu B, Li X, Sun R, Tong X, Ling B, Tian Z, et al. Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface . Proc Natl Acad Sci U S A. 2013; 110: E231-40.

[49]

Makhseed M, Raghupathy R, Azizieh F, Omu A, Al-Shamali E, Ashkanani L. Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and with subsequent abortions. Hum Reprod. 2001; 16: 2219-26.

[50]

Nadeau-Vallée M, Obari D, Palacios J, Brien , Duval C, Chemtob S, et al. Sterile inflammation and pregnancy complications: a review. Reproduction. 2016; 152: R277-92.

[51]

Tersigni C, Neri C, D’Ippolito S, Garofalo S, Martino C, Lanzone A, et al. Impact of maternal obesity on the risk of preterm delivery: insights into pathogenic mechanisms. J Matern Fetal Neonatal Med. 2022; 35: 3216-21.

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