Inteleukin-6 secretion during pathophysiological events of pregnancy – preterm birth, preeclampsia, fetal growth restriction, gestational diabetes mellitus

Anna Pioch; Wiesław Markwitz; Angelika Litwin; Agata Szpera

doi:10.20883/medical.e984

Authors

Anna Pioch Department of Perinatology, Poznan University of Medical Sciences, Poland https://orcid.org/0009-0007-7610-6214
Wiesław Markwitz Department of Perinatology, Poznan University of Medical Sciences, Poland https://orcid.org/0000-0002-2220-8414
Angelika Litwin Department of Gynecology and Oncology, Jagiellonian University Medical College, Cracow, Poland https://orcid.org/0009-0003-9519-4839
Agata Szpera Department of Perinatology, Poznan University of Medical Sciences, Poland https://orcid.org/0000-0002-5546-4799

DOI:

https://doi.org/10.20883/medical.e984

Keywords:

amniotic fluid, cervicovaginal fluid, amniotic cavity, cytokines

Abstract

Cytokines play a role in nearly all reproductive and pregnancy processes. These proteins are expressed in various body fluids and tissues related to reproduction. Interleukin-6 (IL-6) stands out as one of the best-characterized members of the cytokine family. This protein has an immense and imperfectly understood impact on both normal and pathological aspects of human pregnancy. IL-6 exerts a wide range of effects on the immune system, and it plays crucial roles in regulating inflammation processes and homeostasis. Herein, we summarize current knowledge on IL-6 secretion during pathophysiological events of pregnancy: preterm birth, preeclampsia, fetal growth restriction and gestational diabetes mellitus. Cytokines, particularly interleukin-6, play crucial roles in regulating pregnancy physiology. Maintaining IL-6 homeostasis is essential for the health of both the mother and fetus. IL-6 supports pregnancy by influencing uterine receptivity, trophoblast function, and immune interactions at the feto–maternal interface. Disrupted IL-6 expression may contribute to various pregnancy complications. A deeper understanding of IL-6 regulation can help detect dysregulation and potentially optimizing pregnancy outcomes. Addressing knowledge gaps identified in this review is vital for improving current practices and enhancing pregnancy outcomes.

Downloads

Download data is not yet available.

References

Elmslie RE, Dow SW, Ogilvie GK. Interleukins: biological properties and therapeutic potential. J Vet Intern Med. 1991 Sep-Oct;5(5):283-93. doi: 10.1111/j.1939-1676.1991.tb03135.x. DOI: https://doi.org/10.1111/j.1939-1676.1991.tb03135.x

Holmström E, Myntti T, Sorsa T, Kruit H, Juhila J, Paavonen J, Rahkonen L, Stefanovic V. Cervical and Amniotic Fluid Matrix Metalloproteinase-8 and Interleukin-6 Concentrations in Preterm Pregnancies with or without Preterm Premature Rupture of Membranes. Fetal Diagn Ther. 2019;46(2):103-110. doi: 10.1159/000493207. DOI: https://doi.org/10.1159/000493207

Romero R, Espinoza J, Gonçalves LF, Kusanovic JP, Friel LA, Nien JK. Inflammation in preterm and term labour and delivery. Semin Fetal Neonatal Med. 2006 Oct;11(5):317-26. doi: 10.1016/j.siny.2006.05.001. DOI: https://doi.org/10.1016/j.siny.2006.05.001

Del Barco E, Franco-Jarava C, Vargas M, Maíz N, Arevalo S, Sánchez MÁ, Avilés MT, Rodó C, Mendoza M, Goya M, Hernández-González M, Carreras E. Reference values for interleukin-6 in the amniotic fluid of asymptomatic pregnant women. Acta Obstet Gynecol Scand. 2023 Apr;102(4):480-485. doi: 10.1111/aogs.14524. DOI: https://doi.org/10.1111/aogs.14524

Kirici P, Cagiran FT, Kali Z. Impact of spontaneous preterm birth on amniotic fluid NF-κB, IL-6, TNF-α and IL-1β levels in singleton pregnancies conceived after IVF/ICSI treatment or natural conception. Eur Rev Med Pharmacol Sci. 2022 Nov;26(22):8395-8400. doi: 10.26355/eurrev_202211_30374.

Leaños-Miranda A, Nolasco-Leaños AG, Carrillo-Juárez RI, Molina-Pérez CJ, Isordia-Salas I, Ramírez-Valenzuela KL. Interleukin-6 in Amniotic Fluid: A Reliable Marker for Adverse Outcomes in Women in Preterm Labor and Intact Membranes. Fetal Diagn Ther. 2021;48(4):313-320. doi: 10.1159/000514898. DOI: https://doi.org/10.1159/000514898

Heng YJ, Liong S, Permezel M, Rice GE, Di Quinzio MK, Georgiou HM. Human cervicovaginal fluid biomarkers to predict term and preterm labor. Front Physiol. 2015 May 13;6:151. doi: 10.3389/fphys.2015.00151. DOI: https://doi.org/10.3389/fphys.2015.00151

Park S, You YA, Yun H, Choi SJ, Hwang HS, Choi SK, Lee SM, Kim YJ. Cervicovaginal fluid cytokines as predictive markers of preterm birth in symptomatic women. Obstet Gynecol Sci. 2020 Jul;63(4):455-463. doi: 10.5468/ogs.19131. DOI: https://doi.org/10.5468/ogs.19131

Polettini J, Cobo T, Kacerovsky M, Vinturache AE, Laudanski P, Peelen MJ, Helmer H, Lamont RF, Takeda J, Lapointe J, Torloni MR, Zhong N, Menon R. Biomarkers of spontaneous preterm birth: a systematic review of studies using multiplex analysis. J Perinat Med. 2017 Jan 1;45(1):71-84. doi: 10.1515/jpm-2016-0097. DOI: https://doi.org/10.1515/jpm-2016-0097

Soucek O, Kacerovsky M, Kacerovska Musilova I, Stranik J, Kukla R, Bolehovska R, Andrys C. Amniotic fluid CD36 in pregnancies complicated by spontaneous preterm delivery: a retrospective cohort study. J Matern Fetal Neonatal Med. 2023;36(1):2214838. doi: 10.1080/14767058.2023.2214838. DOI: https://doi.org/10.1080/14767058.2023.2214838

Gomez-Lopez N, Galaz J, Miller D, Farias-Jofre M, Liu Z, Arenas-Hernandez M, Garcia-Flores V, Shaffer Z, Greenberg JM, Theis KR, Romero R. The immunobiology of preterm labor and birth: intra-amniotic inflammation or breakdown of maternal-fetal homeostasis. Reproduction. 2022 Jun 20;164(2):R11-R45. doi: 10.1530/REP-22-0046. DOI: https://doi.org/10.1530/REP-22-0046

Amabebe E, Chapman DR, Stern VL, Stafford G, Anumba DOC. Mid-gestational changes in cervicovaginal fluid cytokine levels in asymptomatic pregnant women are predictive markers of inflammation-associated spontaneous preterm birth. J Reprod Immunol. 2018 Apr;126:1-10. doi: 10.1016/j.jri.2018.01.001. DOI: https://doi.org/10.1016/j.jri.2018.01.001

Son KA, Kim M, Kim YM, Kim SH, Choi SJ, Oh SY, Roh CR, Kim JH. Prevalence of vaginal microorganisms among pregnant women according to trimester and association with preterm birth. Obstet Gynecol Sci. 2018 Jan;61(1):38-47. doi: 10.5468/ogs.2018.61.1.38. DOI: https://doi.org/10.5468/ogs.2018.61.1.38

Bogavac M, Brkić S, Celić D, Simin N, Matijasević J, Ilić T. Interferon gamma, interleukin 8 and interleukin 10 in serum of patients with the cervical infection and symptoms of the imminent preterm delivery. Srp Arh Celok Lek. 2013 Sep-Oct;141(9-10):623-8. doi: 10.2298/sarh1310623b. DOI: https://doi.org/10.2298/SARH1310623B

Wassenaar TM, Panigrahi P. Is a foetus developing in a sterile environment? Lett Appl Microbiol. 2014 Dec;59(6):572-9. doi: 10.1111/lam.12334. DOI: https://doi.org/10.1111/lam.12334

Collado MC, Rautava S, Aakko J, Isolauri E, Salminen S. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep. 2016 Mar 22;6:23129. doi: 10.1038/srep23129. DOI: https://doi.org/10.1038/srep23129

Zhu L, Luo F, Hu W, Han Y, Wang Y, Zheng H, Guo X, Qin J. Bacterial Communities in the Womb During Healthy Pregnancy. Front Microbiol. 2018 Sep 6;9:2163. doi: 10.3389/fmicb.2018.02163. DOI: https://doi.org/10.3389/fmicb.2018.02163

Kusanovic JP, Jung E, Romero R, Mittal Green P, Nhan-Chang CL, Vaisbuch E, Erez O, Kim CJ, Gonçalves LF, Espinoza J, Mazaki-Tovi S, Chaiworapongsa T, Diaz-Primera R, Yeo L, Suksai M, Gotsch F, Hassan SS. Characterization of amniotic fluid sludge in preterm and term gestations. J Matern Fetal Neonatal Med. 2022 Dec;35(25):9770-9779. doi: 10.1080/14767058.2022.2053102. DOI: https://doi.org/10.1080/14767058.2022.2053102

Romero R, Gervasi MT, DiGiulio DB, Jung E, Suksai M, Miranda J, Theis KR, Gotsch F, Relman DA. Are bacteria, fungi, and archaea present in the midtrimester amniotic fluid? J Perinat Med. 2023 May 17;51(7):886-890. doi: 10.1515/jpm-2022-0604. DOI: https://doi.org/10.1515/jpm-2022-0604

Kim SA, Park KH, Lee SM, Kim YM, Hong S. Inflammatory Proteins in the Amniotic Fluid, Plasma, and Cervicovaginal Fluid for the Prediction of Intra-Amniotic Infection/Inflammation and Imminent Preterm Birth in Preterm Labor. Am J Perinatol. 2022 May;39(7):766-775. doi: 10.1055/s-0040-1718575. DOI: https://doi.org/10.1055/s-0040-1718575

Park H, Park KH, Kim YM, Kook SY, Jeon SJ, Yoo HN. Plasma inflammatory and immune proteins as predictors of intra-amniotic infection and spontaneous preterm delivery in women with preterm labor: a retrospective study. BMC Pregnancy Childbirth. 2018 May 9;18(1):146. doi: 10.1186/s12884-018-1780-7. DOI: https://doi.org/10.1186/s12884-018-1780-7

Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014 Sep 4;6(10):a016295. doi: 10.1101/cshperspect.a016295. DOI: https://doi.org/10.1101/cshperspect.a016295

Oh KJ, Lee J, Romero R, Park HS, Hong JS, Yoon BH. A new rapid bedside test to diagnose and monitor intraamniotic inflammation in preterm PROM using transcervically collected fluid. Am J Obstet Gynecol. 2020 Sep;223(3):423.e1-423.e15. doi: 10.1016/j.ajog.2020.02.037. DOI: https://doi.org/10.1016/j.ajog.2020.02.037

Balciuniene G, Gulbiniene V, Dumalakiene I, Viliene R, Bartkeviciene D, Pilypiene I, Drasutiene GS, Ramasauskaite D. Prognostic Markers for Chorioamnionitis: IL-6, TNF-α, and MMP-8 in Vaginally Obtained Amniotic Fluid. J Clin Med. 2021 Mar 8;10(5):1136. doi: 10.3390/jcm10051136. DOI: https://doi.org/10.3390/jcm10051136

Ran Y, Huang D, Mei Y, Liu Z, Zhou Y, He J, Zhang H, Yin N, Qi H. Identification of the correlations between interleukin-27 (IL-27) and immune-inflammatory imbalance in preterm birth. Bioengineered. 2021 Dec;12(1):3201-3218. doi: 10.1080/21655979.2021.1945894. DOI: https://doi.org/10.1080/21655979.2021.1945894

Jung EY, Park JW, Ryu A, Lee SY, Cho SH, Park KH. Prediction of impending preterm delivery based on sonographic cervical length and different cytokine levels in cervicovaginal fluid in preterm labor. J Obstet Gynaecol Res. 2016 Feb;42(2):158-65. doi: 10.1111/jog.12882. DOI: https://doi.org/10.1111/jog.12882

Amabebe E, Reynolds S, He X, Wood R, Stern V, Anumba DOC. Infection/inflammation-associated preterm delivery within 14 days of presentation with symptoms of preterm labour: A multivariate predictive model. PLoS One. 2019 Sep 12;14(9):e0222455. doi: 10.1371/journal.pone.0222455. DOI: https://doi.org/10.1371/journal.pone.0222455

Hadzi Lega M, Daneva Markova A, Stefanovic M, Tanturovski M. Interleukin 6 and fetal fibronectin as a predictors of preterm delivery in symptomatic patients. Bosn J Basic Med Sci. 2015 Jan 8;15(1):51-6. doi: 10.17305/bjbms.2015.1.93. DOI: https://doi.org/10.17305/bjbms.2015.1.93

Lee SY, Buhimschi IA, Dulay AT, Ali UA, Zhao G, Abdel-Razeq SS, Bahtiyar MO, Thung SF, Funai EF, Buhimschi CS. IL-6 trans-signaling system in intra-amniotic inflammation, preterm birth, and preterm premature rupture of the membranes. J Immunol. 2011 Mar 1;186(5):3226-36. doi: 10.4049/jimmunol.1003587. DOI: https://doi.org/10.4049/jimmunol.1003587

Marcellin L, Batteux F, Chouzenoux S, Schmitz T, Lorthe E, Mehats C, Goffinet F, Kayem G. Second-trimester amniotic fluid proteins changes in subsequent spontaneous preterm birth. Acta Obstet Gynecol Scand. 2023 May;102(5):597-604. doi: 10.1111/aogs.14544. DOI: https://doi.org/10.1111/aogs.14544

Khedagi AM, Bello NA. Hypertensive Disorders of Pregnancy. Cardiol Clin. 2021 Feb;39(1):77-90. doi: 10.1016/j.ccl.2020.09.005. DOI: https://doi.org/10.1016/j.ccl.2020.09.005

Ovayolu A, Turksoy VA, Ovayolu G, Ozek MA, Dogan I, Karaman E. Analyses of interleukin-6, presepsin and pentraxin-3 in the diagnosis and severity of late-onset preeclampsia. J Matern Fetal Neonatal Med. 2022 Jan;35(2):299-307. doi: 10.1080/14767058.2020.1716718. DOI: https://doi.org/10.1080/14767058.2020.1716718

Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: Pathophysiology, Challenges, and Perspectives. Circ Res. 2019 Mar 29;124(7):1094-1112. doi: 10.1161/CIRCRESAHA.118.313276. Erratum in: Circ Res. 2020 Jan 3;126(1):e8. doi: 10.1161/RES.0000000000000315. DOI: https://doi.org/10.1161/CIRCRESAHA.118.313276

Roberts JM, Escudero C. The placenta in preeclampsia. Pregnancy Hypertens. 2012 Apr 1;2(2):72-83. doi: 10.1016/j.preghy.2012.01.001. DOI: https://doi.org/10.1016/j.preghy.2012.01.001

Lamarca B, Brewer J, Wallace K. IL-6-induced pathophysiology during pre-eclampsia: potential therapeutic role for magnesium sulfate? Int J Interferon Cytokine Mediat Res. 2011 Jul 1;2011(3):59-64. doi: 10.2147/IJICMR.S16320. DOI: https://doi.org/10.2147/IJICMR.S16320

Aggarwal R, Jain AK, Mittal P, Kohli M, Jawanjal P, Rath G. Association of pro- and anti-inflammatory cytokines in preeclampsia. J Clin Lab Anal. 2019 May;33(4):e22834. doi: 10.1002/jcla.22834. DOI: https://doi.org/10.1002/jcla.22834

Tosun M, Celik H, Avci B, Yavuz E, Alper T, Malatyalioğlu E. Maternal and umbilical serum levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in normal pregnancies and in pregnancies complicated by preeclampsia. J Matern Fetal Neonatal Med. 2010 Aug;23(8):880-6. doi: 10.3109/14767051003774942. DOI: https://doi.org/10.3109/14767051003774942

Chen W, Guo Y, Yao X, Zhao D. Correlation of Blood Lipid and Serum Inflammatory Factor Levels With Hypertensive Disorder Complicating Pregnancy. Front Surg. 2022 Jun 17;9:917458. doi: 10.3389/fsurg.2022.917458. DOI: https://doi.org/10.3389/fsurg.2022.917458

Liu Y, Hou X, Yu M, Zhou J. Clinical Analysis of Echocardiography and Serum IL-6 and TNF-α Changes in Pregnant Women with Hypertension. Scanning. 2022 Aug 30;2022:9299746. doi: 10.1155/2022/9299746. Retraction in: Scanning. 2023 Oct 11;2023:9897839. doi: 10.1155/2023/9897839. DOI: https://doi.org/10.1155/2023/9897839

Lumbreras-Marquez MI, Lumbreras-Marquez J, Barraza-Salas M, Castillo-Reyther RA, De la Maza-Labastida S, Hernandez-Rayon YI, Farber MK, Vazquez-Alaniz F. Maternal and umbilical cord procalcitonin, high-sensitivity C-reactive protein, and interleukin-6 levels in preeclamptic and normotensive patients: A cross-sectional study. Pregnancy Hypertens. 2020 Jul;21:218-223. doi: 10.1016/j.preghy.2020.04.009. DOI: https://doi.org/10.1016/j.preghy.2020.04.009

Szarka A, Rigó J Jr, Lázár L, Beko G, Molvarec A. Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array. BMC Immunol. 2010 Dec 2;11:59. doi: 10.1186/1471-2172-11-59. DOI: https://doi.org/10.1186/1471-2172-11-59

Sapmaz E, Çelik A, Bulut V, İlhan F, Hanay F. Preeklampsi Olgularında İnterlökin-6, CRP, Nötrofil ve Platelet Düzeylerinin İncelenmesi. J Clin Obstet Gynecol. 2006;16(6):218-223.

Valencia-Ortega J, Zárate A, Saucedo R, Hernández-Valencia M, Cruz JG, Puello E. Placental Proinflammatory State and Maternal Endothelial Dysfunction in Preeclampsia. Gynecol Obstet Invest. 2019;84(1):12-19. doi: 10.1159/000491087. DOI: https://doi.org/10.1159/000491087

Nzelu D, Dumitrascu-Biris D, Karampitsakos T, Nicolaides KK, Kametas NA. First trimester inflammatory mediators in women with chronic hypertension. Acta Obstet Gynecol Scand. 2020 Sep;99(9):1198-1205. doi: 10.1111/aogs.13857. DOI: https://doi.org/10.1111/aogs.13857

Kara AE, Guney G, Tokmak A, Ozaksit G. The role of inflammatory markers hs-CRP, sialic acid, and IL-6 in the pathogenesis of preeclampsia and intrauterine growth restriction. Eur Cytokine Netw. 2019 Mar 1;30(1):29-33. doi: 10.1684/ecn.2019.0423. DOI: https://doi.org/10.1684/ecn.2019.0423

Staff AC, Johnsen GM, Dechend R, Redman CWG. Preeclampsia and uteroplacental acute atherosis: immune and inflammatory factors. J Reprod Immunol. 2014 Mar;101-102:120-126. doi: 10.1016/j.jri.2013.09.001. DOI: https://doi.org/10.1016/j.jri.2013.09.001

Martinez-Fierro ML, Castruita-De La Rosa C, Garza-Veloz I, Cardiel-Hernandez RM, Espinoza-Juarez MA, Delgado-Enciso I, Castañeda-Lopez ME, Cardenas-Vargas E, Trejo-Vázquez F, Sotelo-Ham EI, Castañeda-Miranda R, Cid-Baez MA, Ortiz-Rodriguez JM, Solis-Sanchez LO, Aviles AG, Ortiz-Castro Y. Early pregnancy protein multiplex screening reflects circulating and urinary divergences associated with the development of preeclampsia. Hypertens Pregnancy. 2018 Feb;37(1):37-50. doi: 10.1080/10641955.2017.1411946. DOI: https://doi.org/10.1080/10641955.2017.1411946

Figueras F, Gratacós E. Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol. Fetal Diagn Ther. 2014;36(2):86-98. doi: 10.1159/000357592. DOI: https://doi.org/10.1159/000357592

Crovetto F, Crispi F, Scazzocchio E, Mercade I, Meler E, Figueras F, Gratacos E. First-trimester screening for early and late small-for-gestational-age neonates using maternal serum biochemistry, blood pressure and uterine artery Doppler. Ultrasound Obstet Gynecol. 2014 Jan;43(1):34-40. doi: 10.1002/uog.12537. DOI: https://doi.org/10.1002/uog.12537

Lausten-Thomsen U, Olsen M, Greisen G, Schmiegelow K. Inflammatory markers in umbilical cord blood from small-for-gestational-age newborns. Fetal Pediatr Pathol. 2014 Apr;33(2):114-8. doi: 10.3109/15513815.2013.879239. DOI: https://doi.org/10.3109/15513815.2013.879239

Yue SL, Eke AC, Vaidya D, Northington FJ, Everett AD, Graham EM. Perinatal blood biomarkers for the identification of brain injury in very low birth weight growth-restricted infants. J Perinatol. 2021 Sep;41(9):2252-2260. doi: 10.1038/s41372-021-01112-8. DOI: https://doi.org/10.1038/s41372-021-01112-8

Alfian I, Chakraborty A, Yong HEJ, Saini S, Lau RWK, Kalionis B, Dimitriadis E, Alfaidy N, Ricardo SD, Samuel CS, Murthi P. The Placental NLRP3 Inflammasome and Its Downstream Targets, Caspase-1 and Interleukin-6, Are Increased in Human Fetal Growth Restriction: Implications for Aberrant Inflammation-Induced Trophoblast Dysfunction. Cells. 2022 Apr 21;11(9):1413. doi: 10.3390/cells11091413. DOI: https://doi.org/10.3390/cells11091413

Al-Azemi M, Raghupathy R, Azizieh F. Pro-inflammatory and anti-inflammatory cytokine profiles in fetal growth restriction. Clin Exp Obstet Gynecol. 2017;44(1):98-103. PMID: 29714875. DOI: https://doi.org/10.12891/ceog3295.2017

de Mendonça ELSS, Fragoso MBT, de Oliveira JM, Xavier JA, Goulart MOF, de Oliveira ACM. Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies. Antioxidants (Basel). 2022 Jan 7;11(1):129. doi: 10.3390/antiox11010129. DOI: https://doi.org/10.3390/antiox11010129

Kim SY, England L, Wilson HG, Bish C, Satten GA, Dietz P. Percentage of gestational diabetes mellitus attributable to overweight and obesity. Am J Public Health. 2010 Jun;100(6):1047-52. doi: 10.2105/AJPH.2009.172890. DOI: https://doi.org/10.2105/AJPH.2009.172890

Choudhury AA, Devi Rajeswari V. Gestational diabetes mellitus - A metabolic and reproductive disorder. Biomed Pharmacother. 2021 Nov;143:112183. doi: 10.1016/j.biopha.2021.112183. DOI: https://doi.org/10.1016/j.biopha.2021.112183

Al-Badri MR, Zantout MS, Azar ST. The role of adipokines in gestational diabetes mellitus. Ther Adv Endocrinol Metab. 2015 Jun;6(3):103-8. doi: 10.1177/2042018815577039. DOI: https://doi.org/10.1177/2042018815577039

Miehle K, Stepan H, Fasshauer M. Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin Endocrinol (Oxf). 2012 Jan;76(1):2-11. doi: 10.1111/j.1365-2265.2011.04234.x. DOI: https://doi.org/10.1111/j.1365-2265.2011.04234.x

Abell SK, De Courten B, Boyle JA, Teede HJ. Inflammatory and Other Biomarkers: Role in Pathophysiology and Prediction of Gestational Diabetes Mellitus. Int J Mol Sci. 2015 Jun 11;16(6):13442-73. doi: 10.3390/ijms160613442. DOI: https://doi.org/10.3390/ijms160613442

Zhang J, Chi H, Xiao H, Tian X, Wang Y, Yun X, Xu Y. Interleukin 6 (IL-6) and Tumor Necrosis Factor α (TNF-α) Single Nucleotide Polymorphisms (SNPs), Inflammation and Metabolism in Gestational Diabetes Mellitus in Inner Mongolia. Med Sci Monit. 2017 Aug 28;23:4149-4157. doi: 10.12659/msm.903565. DOI: https://doi.org/10.12659/MSM.903565

Francis EC, Li M, Hinkle SN, Cao Y, Chen J, Wu J, Zhu Y, Cao H, Kemper K, Rennert L, Williams J, Tsai MY, Chen L, Zhang C. Adipokines in early and mid-pregnancy and subsequent risk of gestational diabetes: a longitudinal study in a multiracial cohort. BMJ Open Diabetes Res Care. 2020 Jul;8(1):e001333. doi: 10.1136/bmjdrc-2020-001333. DOI: https://doi.org/10.1136/bmjdrc-2020-001333

Zhao X, Liu J, Shen L, Wang A, Wang R. Correlation between inflammatory markers (hs-CRP, TNF-α, IL-1β, IL-6, IL-18), glucose intolerance, and gestational diabetes mellitus in pregnant women [Internet]. Vol. 11, Int J Clin Exp Med. 2018. Available from: www.ijcem.com.

Siddiqui S, Waghdhare S, Goel C, Panda M, Soneja H, Sundar J, Banerjee M, Jha S, Dubey S. Augmentation of IL-6 production contributes to development of gestational diabetes mellitus: An Indian study. Diabetes Metab Syndr. 2019 Mar-Apr;13(2):895-899. doi: 10.1016/j.dsx.2018.12.023. DOI: https://doi.org/10.1016/j.dsx.2018.12.023

Xiang LL, Chen C, Wang QY, Zhu YT, Chen YJ, Zeng Y. Impact of inflammatory factors, hemoglobin A1c, and platelet parameters in gestational diabetes mellitus. Arch Gynecol Obstet. 2023 Feb;307(2):439-446. doi: 10.1007/s00404-022-06528-x. DOI: https://doi.org/10.1007/s00404-022-06528-x

Morisset AS, Dubé MC, Côté JA, Robitaille J, Weisnagel SJ, Tchernof A. Circulating interleukin-6 concentrations during and after gestational diabetes mellitus. Acta Obstet Gynecol Scand. 2011 May;90(5):524-30. doi: 10.1111/j.1600-0412.2011.01094.x. DOI: https://doi.org/10.1111/j.1600-0412.2011.01094.x

Kuzmicki M, Telejko B, Szamatowicz J, Zonenberg A, Nikolajuk A, Kretowski A, Gorska M. High resistin and interleukin-6 levels are associated with gestational diabetes mellitus. Gynecol Endocrinol. 2009 Apr;25(4):258-63. doi: 10.1080/09513590802653825. DOI: https://doi.org/10.1080/09513590802653825