Interleukin-6 in pregnancy and gestational disorders

Prins, Jelmer R.; Gomez‐Lopez, Nardhy; Robertson, Sarah A.

doi:10.1016/j.jri.2012.05.004

Cited by 255 publications

(193 citation statements)

References 180 publications

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“…Two strategies were used, an Affymetrix microarray screen as well as detailed analysis of several cytokines. Our experiments show that all three mammalian isoforms of TGF-b (TGF-b1, TGF-b2, and TGF-b3) contribute to eliciting the cervical cell cytokine response to SP, acting via the conventional TGF-b signaling pathway to induce expression of GM-CSF and IL-6, two cytokines with key roles in establishing pregnancy (21,22). Together, these results demonstrate that TGF-b is an important male-female signaling agent implicated in regulating the female immune response to seminal fluid at coitus.…”

mentioning

confidence: 83%

TGF-β Mediates Proinflammatory Seminal Fluid Signaling in Human Cervical Epithelial Cells

Sharkey

Macpherson

Tremellen

et al. 2012

The Journal of Immunology

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150

155

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The cervix is central to the female genital tract immune response to pathogens and foreign male Ags introduced at coitus. Seminal fluid profoundly influences cervical immune function, inducing proinflammatory cytokine synthesis and leukocyte recruitment. In this study, human Ect1 cervical epithelial cells and primary cervical cells were used to investigate agents in human seminal plasma that induce a proinflammatory response. TGF-β1, TGF-β2, and TGF-β3 are abundant in seminal plasma, and Affymetrix microarray revealed that TGF-β3 elicits changes in Ect1 cell expression of several proinflammatory cytokine and chemokine genes, replicating principal aspects of the Ect1 response to seminal plasma. The differentially expressed genes included several induced in the physiological response of the cervix to seminal fluid in vivo. Notably, all three TGF-β isoforms showed comparable ability to induce Ect1 cell expression of mRNA and protein for GM-CSF and IL-6, and TGF-β induced a similar IL-6 and GM-CSF response in primary cervical epithelial cells. TGF-β neutralizing Abs, receptor antagonists, and signaling inhibitors ablated seminal plasma induction of GM-CSF and IL-6, but did not alter IL-8, CCL2 (MCP-1), CCL20 (MIP-3α), or IL-1α production. Several other cytokines present in seminal plasma did not elicit Ect1 cell responses. These data identify all three TGF-β isoforms as key agents in seminal plasma that signal induction of proinflammatory cytokine synthesis in cervical cells. Our findings suggest that TGF-β in the male partner’s seminal fluid may influence cervical immune function after coitus in women, and potentially be a determinant of fertility, as well as defense from infection.

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mentioning

confidence: 83%

TGF-β Mediates Proinflammatory Seminal Fluid Signaling in Human Cervical Epithelial Cells

Sharkey

Macpherson

Tremellen

et al. 2012

The Journal of Immunology

Self Cite

150

155

View full text Add to dashboard Cite

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“…Therefore, the consequences of Th2 polarisation during normal pregnancy include inhibition of cell mediated Th1 cytokines immunity and enhancement of Th2-mediated humoral responses [75]. However, a deregulation of cytokine networks can lead to adverse pregnancy outcomes including spontaneous abortion, preterm labour, pre-eclampsia, and intrauterine growth restriction [76,77]. Such is the case of gestational malaria, in which a pro-inflammatory status has been confirmed and contributes to explain the deleterious effect of P. falciparum infection in mother and fetus [78].…”

Section: Regulation Of the Immune System During Pregnancymentioning

confidence: 99%

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

Maestre

Carmona‐Fonseca

2014

J Infect Dev Ctries

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Women pregnant with their first child are susceptible to severe P. falciparum disease from placental malaria because they lack immunity to placenta-specific cytoadherence proteins. In subsequent pregnancies, as immunity against placental parasites is acquired, there is a reduced risk of adverse effects of malaria on the mother and fetus and asymptomatic parasitaemia is common. In the case of vivax malaria, with increasing reports of severe cases in Asia and South America, the effects of infection by this species during pregnancy remain to be elucidated. This review summarized the main aspects involved in the acquisition of specific antimalarial immune responses during pregnancy with emphasis in research carried out in America and Asia, in order to offer a framework of interpretation for studies on pregnant women with malaria which are recently being produced in these regions. The authors conclude that (1) Effective humoral responses during gestational malaria are mainly directed against variant surface antigens codified by genes of the var2Csa family of P. falciparum; (2) Acquisition of immunity against these variant antigens depends on the degree and intensity of transmission, and the chance increases with age and successive pregnancies; (3) Antibody development is guided by specific cellular immune responses in cases of placental and maternal infection, and (4) The study of the significance of acquisition of specific immunity against both P. falciparum and P. vivax in America, should be performed.

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“…Th e study investigated the serum values of hs-CRP and IL-6 in the fi rst trimester of pregnancy (weeks [10][11][12][13][14] and in the second trimester of pregnancy (weeks [20][21][22][23][24]. Th e samples were analyzed according to the following study protocol: 3 ml blood were collected on anticoagulant, the plasma was separated by centrifugation for 15 min at 1000 xg.…”

Section: Methodsmentioning

confidence: 99%

“…IL-6 is a multifunctional proinfl ammatory cytokine, produced by vascular endothelial cells, the placenta and leukocytes, with a decisive role in infl ammatory response and the control of T cell diff erentiation in adaptive immunity. IL-6 is also involved in trophoblast proli-feration and invasion and in oxidative stress, being the key circulating marker of endothelial dysfunction [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Inflammatory Markers in Pregnant Women at Risk, for the Prediction of Preeclampsia

Oancea

Costin

Pop

et al. 2014

Acta Medica Marisiensis

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Introduction:A low degree of infl ammation has been associated with complications in pregnancies, including preeclampsia (PE). The aim of our study was to determine the serum values of high sensitivity C Reactive Protein (hs-CRP) and Interleukin-6 (IL-6) in the fi rst and second trimesters of pregnancy in pregnant women with risk factors for the development of PE, and to evaluate their relevance for the prediction of this disorder. Material and methods:We performed a prospective longitudinal study on 120 pregnant women, who were divided based on the pregnancy evolution, into two groups: group I -26 pregnant women who developed preeclampsia and group II -94 pregnant women with physiological evolution of pregnancy. Results: Our study has shown an increase in serum levels of hs-CRP and IL-6 in the fi rst and second trimester of pregnancy in patients from group I, signifi cant values being revealed only in the second trimester of pregnancy. The predictive power of the selected infl ammatory markers was signifi cant only for values of hs-CRP in the second trimester of pregnancy, while the association with IL-6 increased the prediction. Conclusions: Increased values of hs-CRP and IL-6 in the second trimester of pregnancy are associated with higher risk for preeclampsia, however the study provided only a modest effi ciency of the prediction capacity.

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Interleukin-6 in pregnancy and gestational disorders

Cited by 255 publications

References 180 publications

TGF-β Mediates Proinflammatory Seminal Fluid Signaling in Human Cervical Epithelial Cells

TGF-β Mediates Proinflammatory Seminal Fluid Signaling in Human Cervical Epithelial Cells

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

Evaluation of Inflammatory Markers in Pregnant Women at Risk, for the Prediction of Preeclampsia

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