IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies

Vilotić, Aleksandra; Nacka-Aleksić, Mirjana; Pirković, Andrea; Bojić‐Trbojević, Žanka; Dekanski, Dragana; Krivokuća, Milica Jovanović

doi:10.3390/ijms232314574

Cited by 67 publications

(36 citation statements)

References 362 publications

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“…Infections or inflammatory conditions, such as COVID-19 during pregnancy, can have a detrimental impact on fetal development and also contribute to pregnancy-associated pathological conditions ( 34 ). Despite the conflicting data regarding the overall profile of IL-6, TNF-α and IFN-γ during healthy pregnancy, there is a consensus that the establishment of a pro-inflammatory microenvironment is associated with the risk of developing pregnancy-associated pathological conditions, including pregnancy loss, preeclampsia, and gestational diabetes mellitus ( 35 ). In this sense, the upregulation of pro-inflammatory cytokines in pregnant women with convalescent COVID-19 may suggest that these patients are more vulnerable to developing adverse pregnancy outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Our data also demonstrated that IL-6 and CXCL8 were included in the set of attributes acquiring strong correlation in the 3 rd pregnancy trimester, named COVID-selective correlations. Implications of IL-6 and CXCL8 in pregnancy-associated pathological conditions, such as pregnancy loss, preeclampsia, gestational diabetes mellitus, and infection/inflammation have been reported ( 35 ). These two soluble mediators are abundantly produced at the feto-maternal interface throughout pregnancy and have been shown to participate in several pregnancy-related events.…”

Section: Discussionmentioning

confidence: 99%

“…These two soluble mediators are abundantly produced at the feto-maternal interface throughout pregnancy and have been shown to participate in several pregnancy-related events. Unbalanced expression/secretion of IL-6 and CXCL8 at the feto-maternal interface has been indicated in unexplained pregnancy loss ( 35 ). A study of the dynamic connections of the soluble mediator network in pre-eclampsia identified positive correlation between IL-6 and CXCL8, suggesting that these molecules are implicated in the pathophysiology of this pregnancy-associated disease ( 35 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

“…Unbalanced expression/secretion of IL-6 and CXCL8 at the feto-maternal interface has been indicated in unexplained pregnancy loss ( 35 ). A study of the dynamic connections of the soluble mediator network in pre-eclampsia identified positive correlation between IL-6 and CXCL8, suggesting that these molecules are implicated in the pathophysiology of this pregnancy-associated disease ( 35 , 49 ). Moreover, a meta-analysis and systematic review suggested a role of CXCL8 in shaping the immune microenvironment in gestational diabetes mellitus ( 50 ).…”

Section: Discussionmentioning

confidence: 99%

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Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study

et al. 2023

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IntroductionSARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators.MethodsA sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array.ResultsIn the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester.Discussion and conclusionFrom an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study

et al. 2023

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“…The review of Vilotić et al [ 3 ] provided a comprehensive overview on the role of IL-6 and IL-8, inflammatory cytokines, in cycling endometrium, the feto–maternal interface, establishment of pregnancy, parturition, and in the pathogenesis of pregnancy-related complications such as pregnancy loss, preeclampsia, gestational diabetes mellitus and infection/inflammation.…”

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confidence: 99%

Pathogenesis of Pregnancy-Related Complications

Hromadníková

2023

IJMS

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Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms

Lipner,

Mac Giollabhui,

Breen

et al. 2024

JAMA Psychiatry

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ImportancePrenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined.ObjectiveTo determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations.Design, Setting, and ParticipantsThis was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023.ExposuresLevels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy.Main Outcomes and MeasuresSelf-reported depressive symptoms at adolescent follow-up.ResultsA total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75).Conclusions and RelevanceIn this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

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IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies

Cited by 67 publications

References 362 publications

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study

Pathogenesis of Pregnancy-Related Complications

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms

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