Tumor Necrosis Factor‐alpha in Gestation and Puerperium of Women with Gestational Hypertension and Pre‐eclampsia

Peraçoli, José Carlos; Rudge, Marilza Vieira Cunha; Peraçoli, Maria Terezinha Serrão

doi:10.1111/j.1600-0897.2006.00455.x

Cited by 90 publications

(73 citation statements)

References 44 publications

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“…[24][25][26] Regarding hypertensive disorders of pregnancy, preeclampsia has been linked to increased serum levels of proinflammatory cytokines, such as IL-6, IL-8, and TNF-α, accompanied by an angiogenic factor imbalance, and for gestational hypertension, increased serum IL-1β, IL-10, and TNF-α has been reported. [27][28][29][30][31][32] Information is limited for early pregnancy; serum IL-1β and TNF-α has been shown elevated before onset of disease in women developing preeclampsia, whereas gestational hypertension has not been separately investigated at early gestation. 33,34 This study aimed to compare disease-specific early gestation serum cytokine profiles of women subsequently developing gestational hypertension or preeclampsia.…”

Section: Tangerås Et Al Cytokines In Hypertensive Pregnancy Disordersmentioning

confidence: 99%

Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia

Tangerås

Austdal

Skråstad

et al. 2015

ATVB

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Objective-Gestational hypertension and preeclampsia involve dysregulated maternal inflammatory responses to pregnancy, but whether such responses differ between the disorders has not been determined. We aimed to investigate disease-specific early pregnancy serum cytokine profiles of women subsequently developing gestational hypertension or preeclampsia for new insight into the underlying pathogeneses and differences between the disorders. Approach and Results-The study cohort consisted of 548 pregnant Norwegian women who were either multiparous with previous gestational hypertension or preeclampsia or were nulliparous. Maternal sera at gestational weeks 11 0 -13 6 were assayed for 27 cytokines, C-reactive protein, total cholesterol, high-density lipoprotein, triglyceride, creatinine, calcium, uric acid, and placental growth factor. Compared with normotensive women, women with both hypertensive conditions presented an atherogenic lipid profile at early gestation, but only those later developing gestational hypertension had significantly higher serum levels of interleukin (IL)-5 and IL-12. Comparing the 2 hypertensive pregnancy disorders, women subsequently developing gestational hypertension had higher serum levels of IL-1β, IL-5, IL-7, IL-8, IL-13, basic fibroblast growth factor, and vascular endothelial growth factor than the women subsequently developing preeclampsia. Conclusions-This study identifies early pregnancy differences in serum cytokine profiles for gestational hypertension and preeclampsia.

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Section: Tangerås Et Al Cytokines In Hypertensive Pregnancy Disordersmentioning

confidence: 99%

Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia

Tangerås

Austdal

Skråstad

et al. 2015

ATVB

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“…This cytokine is a potent and multifunctional proinflammatory Th 1 type cytokine that is involved in the pathogenesis of a large number of autoimmune and inflammatory diseases. Its role has previously been associated with pregnancy pathologies such as PE [12], intrauterine growth restriction [13], gestational diabetes mellitus [14], spontaneous preterm delivery [15] and recurrent abortions [16]. …”

Section: Introductionmentioning

confidence: 99%

TNF-α G308A Gene Polymorphism Has an Impact on Renal Function, Microvascular Permeability, Organ Involvement and Severity of Preeclampsia

Žúbor

Dokus²,

Zigo³

et al. 2014

Gynecol Obstet Invest

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Background/Aims: Preeclampsia (PE) is a life-threatening complication of pregnancy that is associated with a high rate of maternal and perinatal morbidity and/or mortality worldwide. If untreated, it can progress to eclampsia, which can result in the death of the mother, the fetus or both. The etiology of PE is still uncertain; however, recently the role of the immune system has gained in importance. The role of tumor necrosis factor-α (TNF-α), a cytokine involved in inflammation processes, has been widely investigated in obstetric disorders. The aims of the present study were to investigate the effect of TNF-α gene G308A (rs1800629) polymorphism on disease risk, renal function, microvascular permeability, endothelial cell dysfunction and organ involvement in women with PE. Methods: Initially, 102 3rd-trimester pregnant women (preeclamptic cases and healthy controls) with singleton pregnancy were invited for participation, of which 76 were genotyped for TNF-α G308A polymorphism and evaluated for plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), fibronectin and TNF-α, which were tested for correlations with the profile of PE. The odds ratio (OR) and 95% confidence intervals obtained from unconditional logistic regression were used to test the association between the TNF-α polymorphism and PE risk. For continuous variables, we applied Student's t test and, for categorical variables, the Pearson χ² or Fisher's exact test. The two-way ANOVA test with Bonferroni correction was used in multivariate analyses. Results: The A allele was more frequent in cases than controls (22.4 vs. 13.2%), which increased disease risk (OR = 2.73). Maternal serum levels of TNF-α, sVCAM-1 and fibronectin were significantly increased in cases (855.8 ± 385.1 pg/ml, 1,243 ± 671 ng/ml, 0.308 ± 0.231 g/l, respectively) compared to controls (301.1 ± 156.1 pg/ml, 651 ± 250 ng/ml, 0.218 ± 0.101 g/l, respectively; p < 0.0001, p < 0.0001 and p = 0.031, respectively), and these levels showed an increasing trend with the mutant allele genotype. Moderate and severe proteinuria was higher in rs1800629 allele A subjects compared to G/G carriers (53.8 vs. 14.3% (p < 0.05) and 13.0 vs. 4.7% (p < 0.01), respectively). The adverse effect of rs1800629 allele A on renal function was confirmed by increased plasma creatine levels, urinary protein excretion and lower tubular resorption rate in preeclamptic patients. Moreover, rs1800629 allele A preeclamptic carriers showed higher serum levels of fibronectin and sVCAM-1 compared to G/G homozygotes. Conclusion: This study reveals a possible association between clinical and laboratory manifestations of PE and the TNF-α gene G308A (rs1800629) polymorphism.

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“…6,7 A number of variables, such as maternal body mass index (BMI) and age are controversially discussed to influence maternal TNF-α levels during pregnancy, whereas increased TNF-α is associated with a number of adverse pregnancy conditions including gestational hypertension and gestational diabetes mellitus (GDM). 7,8 Elevated TNF-α levels during distressed pregnancies have been suggested to affect trophoblast biology including migratory activity, syncytialization, and endocrine function. 9,10 Moreover, elevated TNF-α may influence the fetal-maternal cross-talk by provoking a shift in the secretory profile of placenta-derived immunemodulating factors, which in turn influences the activity of maternal immune cells.…”

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confidence: 99%

TNF-α alters the inflammatory secretion profile of human first trimester placenta

Siwetz

Blaschitz

El‐Heliebi

et al. 2016

Laboratory Investigation

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Implantation and subsequent placental development depend on a well-orchestrated interaction between fetal and maternal tissues, involving a fine balanced synergistic cross-talk of inflammatory and immune-modulating factors. Tumor necrosis factor (TNF)-α has been increasingly recognized as pivotal factor for successful pregnancy, although high maternal TNF-α levels are associated with a number of adverse pregnancy conditions including gestational hypertension and gestational diabetes mellitus. This study describes effects of exogenously applied TNF-α, mimicking increased maternal TNF-α levels, on the secretion profile of inflammation associated factors in human first trimester villous placenta. Conditioned culture media from first trimester villous placental explants were analyzed by inflammation antibody arrays and ELISA after 48 h culture in the presence or absence of TNF-α. Inflammation antibody arrays identified interleukin (IL)-6, IL-8, chemokine (C-C motif) ligand 2 (CCL2), CCL4, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as the most abundantly secreted inflammation-associated factors under basal culture conditions. In the presence of TNF-α, secretion of GM-CSF, CCL5, and IL-10 increased, whereas IL-4 and macrophage CSF levels decreased compared with controls. ELISA analysis verified antibody arrays by showing significantly increased synthesis and release of GM-CSF and CCL5 by placental explants in response to TNF-α. Immunohistochemistry localized GM-CSF in the villous trophoblast compartment, whereas CCL5 was detected in maternal platelets adhering to perivillous fibrin deposits on the villous surface. mRNA-based in situ padlock probe approach localized GM-CSF and CCL5 transcripts in the villous trophoblast layer and the villous stroma. Results from this study suggest that the inflammatory secretion profile of human first trimester placenta shifts towards increased levels of GM-CSF, CCL5, and IL10 in response to elevated maternal TNF-α levels, whereas IL-6 and IL-8 remain unaffected. This shift may represent a protective mechanism by human first trimester villous placenta to sustain trophoblast function and dampen inflammatory processes in the intervillous space. Implantation and subsequent placenta development are mandatory steps for successful human pregnancy and depend on a well-orchestrated interaction between fetal and maternal tissues. Fetal-maternal interaction involves a fine balanced synergistic cross-talk of inflammaory and immune-modulating factors to allow maternal immune adaption and tolerance of the semiallogeneic fetus at the one hand, whereas maternal immune functions need to be maintained to fight off infections on the other hand. Various concepts and paradigms have been suggested trying to explain how the maternal immune system is modulated to guarantee a viable pregnancy. One of the proposed paradigms is based on studies by Wegmann et al, 1 describing a shift from an inflammatory T-helper 1 (Th1) cytokine profile to a rather anti-inflammatory T-helper 2 (Th2) profile. ...

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Tumor Necrosis Factor‐alpha in Gestation and Puerperium of Women with Gestational Hypertension and Pre‐eclampsia

Abstract: In vivo monocyte activation in GH and PE pregnant women was characterized by in vitro TNF-alpha production. The fact that higher circulating concentrations of TNF-alpha and uric acid were observed in PE than in GH suggests an association with disease severity.

Cited by 90 publications

References 44 publications

Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia

Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia

TNF-α G308A Gene Polymorphism Has an Impact on Renal Function, Microvascular Permeability, Organ Involvement and Severity of Preeclampsia

TNF-α alters the inflammatory secretion profile of human first trimester placenta

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