Interleukin-18 and Interferon Gamma Levels in Preeclampsia: A Systematic Review and Meta-analysis

Yang, Yan; Su, Xiaowei; Xu, Wenming; Zhou, Rong

doi:10.1111/aji.12298

Cited by 37 publications

(24 citation statements)

References 49 publications

(132 reference statements)

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“…The pro-inflammatory cytokine, interferon gamma (Ozkan et al, 2014; Yang et al, 2014) has been reported to be increased in the circulation (plasma and serum) of preeclampsia patients. Additionally, patients with temporal lobe epilepsy have also been reported to have increased levels of interferon gamma (Vieira et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Magnesium Sulfate Prevents Placental Ischemia-Induced Increases in Brain Water Content and Cerebrospinal Fluid Cytokines in Pregnant Rats

Zhang

Warrington

2016

Front. Neurosci.

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Magnesium sulfate (MgSO4) is the most widely used therapy in the clinic to prevent the progression of preeclampsia, a hypertensive disorder of pregnancy, to eclampsia. Eclampsia, manifested as unexplained seizures and/or coma during pregnancy or postpartum, accounts for ~13% of maternal deaths worldwide. While MgSO4 continues to be used in the clinic, the mechanisms by which it exerts its protective actions are not well understood. In this study, we tested the hypothesis that MgSO4 protects against placental ischemia-induced increases in brain water content and cerebrospinal fluid cytokines. To test this hypothesis, MgSO4 was administered via mini-osmotic pump (60 mg/day, i.p.) to pregnant and placental ischemic rats, induced by mechanical reduction of uterine perfusion pressure, from gestational day 14–19. This treatment regimen of MgSO4 led to therapeutic level of 2.8 ± 0.6 mmol/L Mg in plasma. MgSO4 had no effect on improving placental ischemia-induced changes in mean arterial pressure, number of live fetuses, or fetal and placental weight. Placental ischemia increased, while MgSO4 prevented the increase in water content in the anterior cerebrum. Cytokine and chemokine levels were measured in the cerebrospinal fluid using a multi-plex assay. Results demonstrate that cerebrospinal fluid, obtained via the cisterna magna, had reduced protein, albumin, interleukin (IL)-17A, IL-18, IL-2, eotaxin, fractalkine, interferon gamma, vascular endothelial growth factor (VEGF), and macrophage inflammatory protein (MIP)-2 following MgSO4 treatment. These data support the hypothesis that MgSO4 offers neuroprotection by preventing placental ischemia-induced cerebral edema and reducing levels of cytokines/chemokines in the cerebrospinal fluid.

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Section: Discussionmentioning

confidence: 99%

Magnesium Sulfate Prevents Placental Ischemia-Induced Increases in Brain Water Content and Cerebrospinal Fluid Cytokines in Pregnant Rats

Zhang

Warrington

2016

Front. Neurosci.

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“…In a meta-analysis of 16 studies looking at maternal plasma and serum in normal and PE pregnancies by Yang et al (Yang et al 2014), there was a significant trend in the literature for increased interferon (INF)γ levels in PE pregnancies. In 5 independent studies, however, there was no difference observed.…”

Section: Hormones Of Preeclampsia-related Endothelial Dysfunctionmentioning

confidence: 99%

Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

Boeldt

Bird

2017

Journal of Endocrinology

249

152

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Maternal vascular adaptation to pregnancy is critically important in order to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones with directly impact endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy but have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+ signaling events and chronically promoting the breakdown of endothelial cell-cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming more clear. We then describe in detail how the complex endocrine environment of PE effects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.

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“…In the recently published meta‐analysis by Yang et al, nine studies that measured IL‐18 serum levels in PE and normotensive women were included: Studies were based on third‐trimester blood samples, and MD values were not significantly different between PE and controls (95% CI: [−0.4‐0.53], I 2 = 89.1%). In the same review, another two studies assessed but not included, concluded to similar results.…”

Section: Resultsmentioning

confidence: 99%

The role of interleukins in preeclampsia: A comprehensive review

Bellos

Karageorgiou

Kapnias

et al. 2018

American J Rep Immunol

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Preeclampsia is a multi‐system hypertensive disorder of pregnancy, with significant rates of maternal and neonatal morbidity. It represents a major cause of preterm birth, as definitive treatment demands fetal delivery. Although its pathophysiology is complicated, placental hypoxia and endothelial dysfunction constitute established pathogenetic steps of the disease. Inflammation is considered to be a crucial mediator of preeclampsia process, as an imbalance between TH1, TH2, and TH17 immune responses is observed. The present review accumulates current knowledge about the contribution of interleukins in preeclampsia, summarizing the pathways through which each interleukin exerts its function in the disease. Also, the role of genetic polymorphisms is explored and the predictive efficacy of maternal serum interleukin levels is evaluated. Finally, recommendations about the safe interpretation of the outcomes, as well as guidance for future research, are provided.

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Interleukin-18 and Interferon Gamma Levels in Preeclampsia: A Systematic Review and Meta-analysis

Abstract: This meta-analysis suggests that circulating higher IFN-γ levels may be associated with preeclampsia.

Cited by 37 publications

References 49 publications

Magnesium Sulfate Prevents Placental Ischemia-Induced Increases in Brain Water Content and Cerebrospinal Fluid Cytokines in Pregnant Rats

Magnesium Sulfate Prevents Placental Ischemia-Induced Increases in Brain Water Content and Cerebrospinal Fluid Cytokines in Pregnant Rats

Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

The role of interleukins in preeclampsia: A comprehensive review

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