Objective: To evaluate the placental and decidual gene expression and maternal and umbilical serum concentrations of tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, IL-10, IL-1 receptor antagonist (IL-1RA), intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1), along with the proinflammatory/anti-inflammatory cytokine ratios in women with preeclampsia (PE) vs. women with normal pregnancy (NP), and to analyze PE classified as early- (EO) and late-onset (LO). Methods: This cross-sectional study was performed with 50 women with PE (EO n = 30, LO n = 20) and 50 women with NP. Tissue gene expression levels were measured by real-time RT-PCR. Cytokines and adhesion molecules serum concentrations were measured by immunoassays. Results: In PE, placental expression of IL-10 and IL-1RA was lower, while placental IL-8/IL-1RA ratio and maternal concentrations of VCAM-1 were higher vs. NP. In EO, placental expression of IL-10 was lower, while placental IL-8/IL-10 and IL-8/IL-1RA ratios were higher than LO and NP. Maternal concentrations of IL-6 were higher in LO than EO and NP. Throughout PE, maternal VCAM-1 concentrations were higher vs. NP. No significant differences were observed in the decidual expression and umbilical concentrations of the markers between the groups. Conclusion: PE associates with a proinflammatory placental state; however, EO associates with a proinflammatory placental state, while LO associates with systemic maternal inflammation. Both subtypes associated with maternal endothelial dysfunction.

1.
Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF: WHO analysis of causes of maternal death: a systematic review. Lancet 2006; 367: 1066–1074.
2.
Duley L: The global impact of pre-eclampsia and eclampsia. Semin Perinatol 2009; 33: 130–137.
3.
Zárate A, Saucedo R, Valencia J, Manuel L, Hernández M: Early disturbed placental ischemia and hypoxia creates immune alteration and vascular disorder causing preeclampsia. Arch Med Res 2014; 45: 519–524.
4.
American College of Obstetricians and Gynecologists: Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Washington, American College of Obstetricians and Gynecologists, 2013.
5.
Raghupathy R: Cytokines as key players in the pathophysiology of preeclampsia. Med Princ Pract 2013; 22: 8–19.
6.
Catarino C, Santos-Silva A, Belo L, et al: Inflammatory disturbances in preeclampsia: relationship between maternal and umbilical cord blood. J Pregnancy 2012; 2012: 684384.
7.
Pober JS, Sessa WC: Evolving functions of endothelial cells in inflammation. Nature Rev Immunol 2007; 7: 803–815.
8.
Lisonkova S, Joseph KS: Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol 2013; 209: 544.e1–544.e12
9.
Pinheiro CC, Rayol P, Gozzani L, et al: The relationship of angiogenic factors to maternal and neonatal manifestations of early-onset and late-onset preeclampsia. Prenat Diagn 2014; 34: 1084–1092.
10.
Marusic J, Prusac IK, Tomas SZ, Karara JR, Roje D: Expression of inflammatory cytokines in placentas from pregnancies complicated with preeclampsia and HELLP syndrome. J Matern Fetal Neonatal Med 2013; 26: 680–685.
11.
Benyo DF, Smarason A, Redman CW, Sims C, Conrad KP: Expression of inflammatory cytokines in placentas from women with preeclampsia. J Clin Endocrinol Metab 2001; 86: 2505–2512.
12.
Weel IC, Baergen RN, Romão-Veiga M, et al: Association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia. PLoS One 2016; 11: 1–15.
13.
Sun L, Mao D, Cai Y, et al: Association between higher expression of interleukin-8 (IL-8) and haplotype -353A/-251A/+678T of IL-8 gene with preeclampsia. Medicine (Baltimore) 2016; 95:e5537.
14.
Makris A, Xu B, Yu B, Thornton C, Hennessy A: Placental deficiency of interleukin-10 (IL-10) in preeclampsia and its relationship to an IL10 promoter polymorphism. Placenta 2006; 27: 445–451.
15.
Goksu AY, Nazli M, Elis S: Significance of platelet endothelial cell adhesion molecule-1 (PECAM-1) and intercellular adhesion molecule-1 (ICAM-1) expressions in preeclamptic placentae. Endocrine 2012; 42: 125–131.
16.
Jaakkola K, Jokimaa V, Kallajoki M, Jalkanen S, Ekholm E: Pre-eclampsia does not change the adhesión molecule status in the placental bed. Placenta 2000; 21: 133–141.
17.
Tziotis J, Malamitsi-Puchner A, Vlachos G, Creatsas G, Michalas S: Adhesion molecules expression in the placental bed of pregnancies with pre-eclampsia. Br J Obstet Gynaecol 2002; 109: 197–201.
18.
Zhu H, Hou CC, Luo LF, Hu YJ, Yang WX: Endometrial stromal cells and decidualized stromal cells: Origins, transformation and functions. Gene 2014; 551: 1–14.
19.
Wilczynski JR, Tchórzewski H, Banasik M, et al: Lymphocyte subset distribution and cytokine secretion in third trimester decidua in normal pregnancy and preeclampsia. Eur J Obstet Gynecol Reprod Biol 2003; 109: 8–15.
20.
Lockwood CJ, Yen CF, Basar M, et al: Preeclampsia-related inflammatory cytokines regulate interleukin-6 expression in human decidual cells. Am J Pathol 2008; 172: 1571–1579.
21.
Molvarec A, Szarka A, Walentin S, et al: Serum leptin levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in normal pregnancy and preeclampsia. Reprod Biol Endocrinol 2011; 9: 1–9.
22.
Sharma A, Satyam A, JB Sharma: Leptin, IL-10 and inflammatory markers (TNF-alpha, IL-6 and IL-8) in pre-eclamptic, normotensive pregnant and healthy non-pregnant women. Am J Reprod Immunol 2007; 58: 21–30.
23.
Benian A, Madazl? R, Aksu F, Uzun H, Aydin S: Plasma and Placental Levels of Interleukin-10, Transforming Growth Factor-beta1, and Epithelial-Cadherin in Preeclampsia. Obstet Gynecol 2002; 100: 327–331.
24.
Ozler A, Turgut A, Sak ME, et al: Serum levels of neopterin, tumor necrosis factor-alpha and interleukin-6 in preeclampsia: relationship with disease severity. Eur Rev Med Pharmacol Sci 2012; 16: 1707–1712.
25.
Maharaj IR, Phulukdaree A, Nagiah S, Ramkaran P, Tiloke C, Chuturgoon AA: Pro-inflammatory cytokine levels in HIV infected and uninfected pregnant women with and without preeclampsia. PLoS One 2017; 12: 1–9.
26.
Afshari JT, Ghomian N, Shameli A, et al: Determination of Interleukin-6 and Tumor Necrosis Factor-alpha concentrations in Iranian-Khorasanian patients with preeclampsia. BMG Pregnancy Childbirth 2005; 5: 1–5.
27.
Pinheiro MB, Olindo A, Martins-Filho, et al: Severe preeclampsia goes along with a cytokine network disturbance towards a systemic inflammatory state. Cytokine 2013; 62: 165–173.
28.
Moreno-Eutimio MA, Tovar-Rodríguez JM, Vargas-Avila K, et al: Increased serum levels of inflammatory mediators and low frequency of regulatory T cells in the peripheral blood of preeclamptic Mexican women. Biomed Res Int 2014; 2014: 413249.
29.
Kim SY, Ryu HM, Yang JH, et al: Maternal Serum Levels of VCAM-1, ICAM-1 and E-selectin in preeclampsia. J Korean Med Sci 2004; 19: 688–692.
30.
Rios DR, Alpoim PN, Godoi LC, et al: Increased Levels of sENG and sVCAM-1 and decreased levels of VEGF in severe preeclampsia. Am J Hypertens 2016; 29: 1307–1310.
31.
Tosun M, Celik H, Avci B, Yavuz E, Alper T, Malatyalioqlu E: Maternal and umbilical serum levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in normal pregnancies and in pregnancies complicated by preeclampsia. J Matern Fetal Neonatal Med 2010; 23: 880–886.
32.
Krauss T, Azab H, Dietrich M, Augustin HG: Fetal plasma levels of circulating endothelial cell adhesion molecules in normal and preeclamptic pregnancies. Eur J Obstet Gynecol Reprod Biol 1998; 78: 41–45.
33.
Dogan E, Demir SC, Gulec UK. Maternal soluble vascular cytoplasmic adhesion molecule-1 and fibronectin levels in early- and late-onset preeclamptic pregnancies. Clin Exp Obstet Gynecol 2014; 41: 681–684.
34.
Raymond D, Peterson E: A critical review of early-onset and late-onset preeclampsia. Obstet Gynecol Surv 2011; 66: 497–506.
35.
Nelson DB, Ziadie MS, McIntire DD, et al: Placental pathology suggesting that preeclampsia is more than one disease. Am J Obstet Gynecol 2014; 210: 66.e1–66.e7.
36.
Ferguson KK, Meeker JD, McElrath TM, et al: Repeated measures of inflammation and oxidative stress biomarkers in preeclamptic and normotensive pregnancies. Am J Obstet Gynecol 2017; 216: 527.e1–527.e9.
37.
Amash A, Weintraub AY, Sheiner E, et al: Possible therapeutic effect of magnesium sulfate in pre-eclampsia by the down-regulation of placental tumor necrosis factor-alpha secretion. Eur Cytokine Netw 2010; 21: 58–64.
38.
Amash A, Holcberg G, Sheiner E, et al: Magnesium sulfate normalizes placental interleukin-6 secretion in preeclampsia. J Interferon Cytokine Res 2010; 30: 683–690.
39.
Amash A, Holcberg G, Sapir O, et al: Placental secretion of interleukin-1 and interleukin-1 receptor antagonist in preeclampsia: effect of magnesium sulfate. J Interferon Cytokine Res 2012; 32: 432–441.
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