Exploration of Immunology

Table 4. Previous studies showing the effect of various cytokines including IL-6, IL-10, and the ratio (IL-6/IL-10) in RPL

Author and year/reference	Title	Results	Ethnicity	IL-6	IL-10	IL-6/IL-10
Bates et al., 2002 [44]	Aberrant cytokine production by peripheral blood mononuclear cells in recurrent pregnancy loss?	This study showed increased IL-10 levels in pregnant women compared with non-pregnant controls, and further increased in RPL patients (p = 0.026).	Europe	ND	↑	ND
Daher et al., 2004 [10]	Cytokines in recurrent pregnancy loss	This study comprised 29 women in the RPL group (at least three consecutive spontaneous abortions) and 27 women in the control group (with a history of successful pregnancies and no miscarriage). No significant difference was detected between RPL and control groups in relation to IL-6.	South America	No difference seen	ND	ND
Calleja-Agius et al., 2008 [34]	Recurrent miscarriages: What is the role of cytokines?	In this study, lower levels of IL-6 and IL-10 were found in RPL cases than in normal pregnant women.	Europe	↓	↓	ND
Abdullah et al., 2013 [45]	The role of cytokines among women with spontaneous miscarriage	This study enrolled 46 women as the patient group with first-trimester miscarriage and 38 women as the control group with first-trimester successful pregnancy with no history of miscarriage. There were significantly higher levels of IL-10 in the aborted women as compared to the controls, and no significant difference was detected between women with miscarriage and control groups in relation to IL-6.	Asia	No difference seen	↑	ND
Pandey et al., 2017 [40]	Interplay of cytokines in preterm birth	This study highlights the association of cytokine gene polymorphisms and their levels with preterm birth. Increased maternal levels of IL-6 and low levels of IL-10 have been found to be associated with preterm birth.	Asia	↑	↓	ND
Tyagi et al., 2020 [41]	Evaluation of Pro-inflammatory Cytokine Level in Cases of Idiopathic Recurrent Spontaneous Miscarriage in Saudi Arabia	This study comprised Group I—pregnant women with a history of recurrent spontaneous miscarriage (RSM, n = 50) and Group II—healthy pregnant controls (n = 50). IL-6 was found to be decreased in Group I patients (p < 0.001) as compared with the normal control Group II.	Saudi Arabia	↓	ND	ND
Vilotić et al., 2022 [35]	IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies	According to the reviewed literature, IL-6 appears to contribute to the establishment and maintenance of pregnancy by mediating uterine receptivity, trophoblast function at the implantation site and parturition, the immune-endocrine interactions at the feto-maternal interface, and other processes. Increased IL-6 expression in decidual tissues in RPL, compared to normal pregnancy, was found.	Europe	↑	ND	ND
Our findings—2025	Association of circulating IL-6 and IL-10 levels during mid-gestation with recurrent pregnancy loss history and severity: a South Indian study	This study comprised a total of 170 pregnant women with (RPL, n = 85) and without (NRPL, n = 85) a history of RPL during the second trimester of pregnancy. The RPL group was further divided into women with 2 and > 2 previous pregnancy losses. Increased levels of IL-6 and IL-6/IL-10 ratio and decreased levels of IL-10 were found in the RPL group compared to the NRPL group.	Asia	↑	↓	↑

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IL-6: interleukin-6; RPL: recurrent pregnancy loss; NRPL: non-recurrent pregnancy loss; ↑: increased in RPL; ↓: decreased in RPL; ND: not defined

Declarations

Acknowledgments

We are grateful to Dr. Rajeshwari Bonu, Gynaecologist, Niloufer Government Maternity Hospital, Hyderabad, India, for giving us the opportunity to carry forward our research by providing blood samples, and we express gratitude to the blood donors for their cooperation in sharing their clinical data.

Author contributions

SJ: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing—original draft, Writing—review & editing. RB: Data curation, Investigation. PJ: Conceptualization, Project administration, Supervision, Funding acquisition, Resources, Formal analysis, Writing—review & editing.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The present study has approval from the Ethical Committee (Reg. No. ECR/300/Inst/AP/2013/RR-16), Osmania Medical College, Hyderabad, Telangana state, India, and informed consent from the study subjects. This study complies with the 2013 version of the Declaration of Helsinki.

Consent to participate

Informed consent to participate in the study was obtained from all participants.

Consent to publication

Not applicable.

Availability of data and materials

The preprint for this study is available on Authorea. The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

Funding

The authors have received research funding from the Indian Council of Medical Research, New Delhi, India [ICMR, Id No.: 2019–1022]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

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