The role of interleukins in preeclampsia: A comprehensive review

Bellos, Ioannis; Karageorgiou, Vasilios; Kapnias, Dimitrios; Karamanli, Konstantina-Eleni; Siristatidis, Charalampos

doi:10.1111/aji.13055

Cited by 57 publications

(40 citation statements)

References 216 publications

(282 reference statements)

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“…Moreover, acute atherosis has been linked to increased oxidative stress and lipid content in the decidua of preeclamptic women . Oxidative stress is also implicated in the pathophysiology of preeclampsia and fetal growth restriction . Hence, we proposed that macrophages are implicated in the mechanisms leading to oxidative stress, and therefore, obstetrical disease (ie, acute atherosis).…”

Section: Discussionmentioning

confidence: 99%

The immunophenotype of decidual macrophages in acute atherosis

Gill

Leng

Romero

et al. 2019

American J Rep Immunol

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Problem: Acute atherosis is a uteroplacental arterial lesion that is associated with pregnancy complications such as preeclampsia and preterm birth, the latter being the leading cause of perinatal morbidity and mortality worldwide. However, the immunobiology of acute atherosis is poorly understood. Method of study:Placental basal plate samples were collected from women who delivered with (n = 11) and without (n = 31) decidua basalis lesions of acute atherosis.Multicolor flow cytometry was used to quantify M1-and M2-like macrophage subsets and the expression of iNOS and IL-12 by decidual macrophages. Multiplex fluorescence staining and phenoptics were performed to localize M1-, MOX-, and Mhem-like macrophages in the decidual basalis. Results:Macrophages displayed diverse phenotypes in the decidua basalis with acute atherosis. M2-like macrophages were the most abundant subset in the decidua; yet, this macrophage subset did not change with the presence of acute atherosis. Decidual M1-like macrophages were increased in acute atherosis, and such macrophages displayed a pro-inflammatory phenotype, as indicated by the expression of iNOS and IL-12. Decidual M1-like pro-inflammatory macrophages were localized near both transformed and non-transformed vessels in the decidua basalis with acute atherosis.

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Section: Discussionmentioning

confidence: 99%

The immunophenotype of decidual macrophages in acute atherosis

Gill

Leng

Romero

et al. 2019

American J Rep Immunol

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“…The pathophysiology of preeclampsia is complex and remains still under investigation. It is hypothesized that poor trophoblast invasion and deficient spiral artery remodeling lead to placental ischemia‐reperfusion injury 4 and the release of various angiogenic, 5 oxidative, 6 and inflammatory 7 mediators into maternal circulation, promoting generalized endothelial dysfunction, increased vascular reactivity, and activation of the coagulation cascade 8 . Risk stratification is essential in order to identify the subpopulation of pregnant women that would benefit from preventive measures early in the course of gestation, especially the administration of aspirin 9 .…”

Section: Introductionmentioning

confidence: 99%

The prognostic role of serum uric acid levels in preeclampsia: A meta‐analysis

Bellos

Pergialiotis

Loutradis

et al. 2020

J of Clinical Hypertension

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This meta-analysis aims to compare serum uric acid levels among preeclamptic and healthy pregnant women across the various trimesters and provide a summary of the effect size of this biomarker in predicting adverse pregnancy outcomes. MEDLINE, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception. Observational studies were held eligible if they reported serum uric acid among preeclamptic and healthy pregnant women. Metaanalysis was conducted regarding uric acid concentration, diagnostic accuracy, and association with perinatal outcomes. The credibility of evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The analysis included 196 studies, comprising 39 540 women.Preeclampsia was associated with significantly elevated uric acid levels during the 1st (mean difference [MD]: 0.21 mg/dL, 95% confidence intervals [CI]: 0.06-0.35) trimester, 2nd (MD: 1.41 mg/dL, 95% CI: 0.78-2.05) trimester, and 3rd (MD: 2.26 mg/dL, 95% CI: 2.12-2.40) trimester. Higher uric acid was estimated for severe preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelet syndrome. The sensitivity for adverse perinatal outcome prediction ranged from 67.3% to 82.7% and the specificity from 47.7% to 70.7%. In conclusion, it is suggested that serum uric acid levels are increased in preeclampsia and can be used to predict disease severity and pregnancy complications. Future prospective studies should verify these outcomes, assess the optimal cutoffs, and incorporate uric acid to combined predicting models. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information may be found online in the Supporting Information section. How to cite this article: Bellos I, Pergialiotis V, Loutradis D, Daskalakis G. The prognostic role of serum uric acid levels in preeclampsia: A meta-analysis. J Clin Hypertens. 2020;22: 826-834. https://doi.

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“…Most APO can trace their origins to placenta, especially to placental inflammation/infection . Pre‐eclampsia and fetal growth restriction are rooted in defects of early placental development and later placental inflammation (the two‐stage model) . Stillbirth and fetal growth restriction are associated with placental inflammation due to infectious or noninfectious causes .…”

Section: Introductionmentioning

confidence: 99%

“…9 Preeclampsia and fetal growth restriction are rooted in defects of early placental development and later placental inflammation (the two-stage model). 9,10 Stillbirth and fetal growth restriction are associated with placental inflammation due to infectious or noninfectious causes. 9 A recent morphological study showed that inflammation/infection and malperfusion were the two most common pathological changes in the placentas of preterm birth.…”

Section: Introductionmentioning

confidence: 99%

A rat model of placental inflammation explains the unexplained elevated maternal serum alpha‐fetoprotein associated with adverse pregnancy outcomes

Zhang

Chan

et al. 2019

J of Obstet and Gynaecol

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Aim It has been reported in numerous studies that elevated maternal serum alpha‐fetoprotein (MS‐AFP) is associated with adverse pregnancy outcomes (APO), such as pre‐eclampsia, stillbirth, preterm birth and fetal growth restriction. However, the mechanism linking elevated MS‐AFP and APO is obscure. In this study, we tried to explore the mechanism by using pregnant rats. Methods Lipopolysaccharide (LPS) was used to induce placental inflammation in pregnant rats. Maternal serum and placental inflammatory cytokines and placental morphology were used to assess the level of placental inflammation. The incidences of APO and the levels of MS‐AFP were evaluated. The expressions of alpha‐fetoprotein (AFP) in the related organs and fetal serum AFP levels were detected. Results Compared to saline‐treated pregnant rats, LPS led to elevated maternal serum and placental inflammatory cytokines and a higher rate of placental inflammation. Lipopolysaccharide resulted in the features of APO and at the same time elevated MS‐AFP. Maternal serum alpha‐fetoprotein levels were significantly correlated to the evaluation parameters of APO. Lipopolysaccharide did not increase the expressions of AFP in fetal liver, maternal liver and placenta, but reduced the fetal serum AFP levels. Conclusion The phenomenon that elevated MS‐AFP is associated with APO, which has been reported in human pregnancies, is observed in our rat model. Placental inflammation can be the potential cause linking the two manifestations together. Although the source of elevated MS‐AFP is not identified, fetal blood circulation is suspected. Our study may provide an animal model for the future studies on this subject.

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The role of interleukins in preeclampsia: A comprehensive review

Cited by 57 publications

References 216 publications

The immunophenotype of decidual macrophages in acute atherosis

The immunophenotype of decidual macrophages in acute atherosis

The prognostic role of serum uric acid levels in preeclampsia: A meta‐analysis

A rat model of placental inflammation explains the unexplained elevated maternal serum alpha‐fetoprotein associated with adverse pregnancy outcomes

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