Antenatal corticosteroids impact the inflammatory rather than the antiangiogenic profile of women with preeclampsia

Unzila A. Nayeri*, Irina A. Buhimschi, Christine A. Laky, Sarah N. Cross, Christina M. Duzyj, Wenda Ramma, Baha M. Sibai, Edmund F. Funai, Asif Ahmed, Catalin S. Buhimschi

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Circulating antiangiogenic factors and proinflammatory cytokines are implicated in the pathogenesis of preeclampsia. This study was performed to test the hypothesis that steroids modify the balance of inflammatory and proangiogenic and antiangiogenic factors that potentially contribute to the patient's evolving clinical state. Seventy singleton women, admitted for antenatal corticosteroid treatment, were enrolled prospectively. The study group consisted of 45 hypertensive women: chronic hypertension (n=6), severe preeclampsia (n=32), and superimposed preeclampsia (n=7). Normotensive women with shortened cervix (<2.5 cm) served as controls (n=25). Maternal blood samples of preeclampsia cases were obtained before steroids and then serially up until delivery. A clinical severity score was designed to clinically monitor disease progression. Serum levels of angiogenic factors (soluble fms-like tyrosine kinase-1 [sFlt-1], placental growth factor [PlGF], soluble endoglin [sEng]), endothelin-1 (ET-1), and proinflammatory markers (IL-6, C-reactive protein [CRP]) were assessed before and after steroids. Soluble IL-2 receptor (sIL-2R) and total immunoglobulins (IgG) were measured as markers of T- and B-cell activation, respectively. Steroid treatment coincided with a transient improvement in clinical manifestations of preeclampsia. A significant decrease in IL-6 and CRP was observed although levels of sIL-2R and IgG remained unchanged. Antenatal corticosteroids did not influence the levels of angiogenic factors but ET-1 levels registered a short-lived increase poststeroids. Although a reduction in specific inflammatory mediators in response to antenatal steroids may account for the transient improvement in clinical signs of preeclampsia, inflammation is unlikely to be the major contributor to severe preeclampsia or useful for therapeutic targeting. © 2014 American Heart Association, Inc.

Original languageEnglish
Pages (from-to)1285-1292
Number of pages8
JournalHypertension
Volume63
Issue number6
Early online date24 Mar 2014
DOIs
Publication statusPublished - 2014

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Pre-Eclampsia
Adrenal Cortex Hormones
Steroids
Interleukin-2 Receptors
Angiogenesis Inducing Agents
Endothelin-1
C-Reactive Protein
Interleukin-6
Immunoglobulin G
Vascular Endothelial Growth Factor Receptor-1
Cervix Uteri
Disease Progression
Immunoglobulins
Intercellular Signaling Peptides and Proteins
B-Lymphocytes
Therapeutics
Mothers
Cytokines
Hypertension
Inflammation

Bibliographical note

Funding: Albert McKern Memorial Fund grant; Yale University Maternal-Fetal Medicine fellowship academic enhancement fund, Center for Perinatal Research Nationwide Children's Hospital; Department of Obstetrics and Gynecology at The Ohio State University; British Heart Foundation; Medical Research Council [MRC Programme Grant (G0700288)].

Data Supplement : http://hyper.ahajournals.org/lookup/suppl/doi:10.1161/HYPERTENSIONAHA.114.03173/-/DC1

Keywords

  • angiogenesis inducing agents
  • inflammation
  • pacenta
  • preeclampsia
  • steroids

Cite this

Nayeri, U. A., Buhimschi, I. A., Laky, C. A., Cross, S. N., Duzyj, C. M., Ramma, W., ... Buhimschi, C. S. (2014). Antenatal corticosteroids impact the inflammatory rather than the antiangiogenic profile of women with preeclampsia. Hypertension, 63(6), 1285-1292. https://doi.org/10.1161/HYPERTENSIONAHA.114.03173
Nayeri, Unzila A. ; Buhimschi, Irina A. ; Laky, Christine A. ; Cross, Sarah N. ; Duzyj, Christina M. ; Ramma, Wenda ; Sibai, Baha M. ; Funai, Edmund F. ; Ahmed, Asif ; Buhimschi, Catalin S. / Antenatal corticosteroids impact the inflammatory rather than the antiangiogenic profile of women with preeclampsia. In: Hypertension. 2014 ; Vol. 63, No. 6. pp. 1285-1292.
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Nayeri, UA, Buhimschi, IA, Laky, CA, Cross, SN, Duzyj, CM, Ramma, W, Sibai, BM, Funai, EF, Ahmed, A & Buhimschi, CS 2014, 'Antenatal corticosteroids impact the inflammatory rather than the antiangiogenic profile of women with preeclampsia', Hypertension, vol. 63, no. 6, pp. 1285-1292. https://doi.org/10.1161/HYPERTENSIONAHA.114.03173

Antenatal corticosteroids impact the inflammatory rather than the antiangiogenic profile of women with preeclampsia. / Nayeri, Unzila A.; Buhimschi, Irina A.; Laky, Christine A.; Cross, Sarah N.; Duzyj, Christina M.; Ramma, Wenda; Sibai, Baha M.; Funai, Edmund F.; Ahmed, Asif; Buhimschi, Catalin S.

In: Hypertension, Vol. 63, No. 6, 2014, p. 1285-1292.

Research output: Contribution to journalArticle

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AU - Buhimschi, Irina A.

AU - Laky, Christine A.

AU - Cross, Sarah N.

AU - Duzyj, Christina M.

AU - Ramma, Wenda

AU - Sibai, Baha M.

AU - Funai, Edmund F.

AU - Ahmed, Asif

AU - Buhimschi, Catalin S.

N1 - Funding: Albert McKern Memorial Fund grant; Yale University Maternal-Fetal Medicine fellowship academic enhancement fund, Center for Perinatal Research Nationwide Children's Hospital; Department of Obstetrics and Gynecology at The Ohio State University; British Heart Foundation; Medical Research Council [MRC Programme Grant (G0700288)]. Data Supplement : http://hyper.ahajournals.org/lookup/suppl/doi:10.1161/HYPERTENSIONAHA.114.03173/-/DC1

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N2 - Circulating antiangiogenic factors and proinflammatory cytokines are implicated in the pathogenesis of preeclampsia. This study was performed to test the hypothesis that steroids modify the balance of inflammatory and proangiogenic and antiangiogenic factors that potentially contribute to the patient's evolving clinical state. Seventy singleton women, admitted for antenatal corticosteroid treatment, were enrolled prospectively. The study group consisted of 45 hypertensive women: chronic hypertension (n=6), severe preeclampsia (n=32), and superimposed preeclampsia (n=7). Normotensive women with shortened cervix (<2.5 cm) served as controls (n=25). Maternal blood samples of preeclampsia cases were obtained before steroids and then serially up until delivery. A clinical severity score was designed to clinically monitor disease progression. Serum levels of angiogenic factors (soluble fms-like tyrosine kinase-1 [sFlt-1], placental growth factor [PlGF], soluble endoglin [sEng]), endothelin-1 (ET-1), and proinflammatory markers (IL-6, C-reactive protein [CRP]) were assessed before and after steroids. Soluble IL-2 receptor (sIL-2R) and total immunoglobulins (IgG) were measured as markers of T- and B-cell activation, respectively. Steroid treatment coincided with a transient improvement in clinical manifestations of preeclampsia. A significant decrease in IL-6 and CRP was observed although levels of sIL-2R and IgG remained unchanged. Antenatal corticosteroids did not influence the levels of angiogenic factors but ET-1 levels registered a short-lived increase poststeroids. Although a reduction in specific inflammatory mediators in response to antenatal steroids may account for the transient improvement in clinical signs of preeclampsia, inflammation is unlikely to be the major contributor to severe preeclampsia or useful for therapeutic targeting. © 2014 American Heart Association, Inc.

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