Increased circulating interleukin-17 levels in preeclampsia

Abstract

Increasing evidence suggests that an exaggerated maternal systemic inflammatory response, as well as an angiogenic imbalance plays a central role in the pathogenesis of preeclampsia. In this study, we determined circulating levels of interleukin-17 (IL-17) along with those of angiogenic factors in healthy non-pregnant and pregnant women and preeclamptic patients, and examined whether serum IL-17 levels of preeclamptic patients were related to their clinical features and angiogenic factor concentrations. Fifty-nine preeclamptic patients, 60healthy pregnant women and 56 healthy non-pregnant women were involved in this casecontrol study. Serum levels of IL-17A were measured by high sensitivity ELISA. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were determined by electrochemiluminescence immunoassay. For statistical analyses, non-parametric methods were applied. Serum IL-17 levels were significantly higher in preeclamptic patients than in healthy non-pregnant and pregnant women. We did not find any relationship between serum IL-17 concentrations of preeclamptic patients and their clinical features and serum sFlt-1 and PlGF levels or sFlt-1/PlGF ratios. However, elevated serum IL-17 level and sFlt-1/PlGF ratio was found to be additive for the risk of preeclampsia, as shown by the substantially higher odds ratios of their combination than of either alone. In conclusion, serum IL-17 levels are increased in preeclampsia, which might contribute to the development of the excessive systemic inflammatory response characteristic of the maternal syndrome of the disease. In addition, elevated serum IL-17 level and sFlt-1/PlGF ratio had an additive (joint) effect in the risk of preeclampsia.

Angiogenic imbalance and diminished matrix metalloproteinase-2 and -9 underlie regional decreases in uteroplacental vascularization and feto-placental growth in hypertensive pregnancy

“…The sFlt-1/PlGF ratio can be modulated by not only sFlt-1, but also PlGF. The present observation that plasma levels of PlGF are decreased in RUPP vs Preg rats is consistent with reports that PlGF levels are decreased in preeclamptic women [29, 33, 36] and in RUPP and Dahl salt-sensitive rat models of HTN-Preg [17, 24, 80, 82]. 2) Because plasma angiogenic factors represent the global release from different maternal tissues, we measured the angiogenic factors in the different regions of the uterus and found that sFlt-1 was increased, PlGF was decreased and sFlt-1/PlGF was increased in the placenta and uterus of proximal, middle and distal regions of the RUPP uterus compared to the corresponding regions in the Preg uterus.…”

“…Angiogenic imbalance could play a role in the observed regional changes in placental and fetal growth, uteroplacental vascularization and MMPs in the Preg and RUPP uterus because: 1) The levels of sFlt-1 and the sFlt-1/PlGF ratio increased in the plasma of RUPP vs Preg rats. The observed increases in plasma sFlt-1 levels and sFlt-1/PlGF ratio in RUPP rats are consistent with reports that circulating sFlt-1 and the sFlt-1/PlGF ratio are elevated in preeclamptic women [29, 33, 35, 36, 77], and in RUPP and other animal models of HTN-Preg [17, 24, 78–82]. The sFlt-1/PlGF ratio can be modulated by not only sFlt-1, but also PlGF.…”

“…Circulating levels of sFlt-1 are 10-fold higher in pregnant than non-pregnant women, remain almost stable during the first and second trimester, then increase after the 36 th week of gestation and throughout the third trimester [20]. The circulating sFlt-1 levels and sFlt-1/PlGF ratio are much higher in preeclamptic than normal pregnant women from the second trimester onwards [25, 29, 33, 35, 36]. These observations suggest that angiogenic imbalance could be a mechanism linking RUPP to HTN-Preg.…”

Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

“…sFlt-1 gene is localized on chromossome 13q12, and an extra copy of this gene in women with trisomy 13 may lead to excess circulating sFlt-1, reduced PlGF and increased risk of PE (Kakigano et al, 2013). Several reports have shown higher circulating levels of sFlt-1 in early and late PE (Tsatsaris et al, 2003; Ramma et al, 2012; Bian et al, 2015; March et al, 2015; Molvarec et al, 2015; Tuzcu et al, 2015). Serum sFlt-1 is also higher in women with previous PE (~0.5 ng/mL) than in women with previous normal pregnancy (~0.3 ng/mL), even 6 months or more after delivery (Tuzcu et al, 2015).…”

“…PlGF levels during 21 and 22 weeks of gestation are ~353 pg/mL, rising steadily during gestation to reach a median level of ~574 pg/mL after 29 and 30 weeks of gestation (Krauss et al, 2004). During PE, circulating PlGF levels decrease (Tsatsaris et al, 2003; Ramma et al, 2012; Bian et al, 2015; Molvarec et al, 2015) and the decrease is more apparent in early than late PE (March et al, 2015). PlGF has four alternatively spliced mRNA species (PIGF 1–4), and its predominant isoform PIGF-1 is downregulated in PE (Bates, 2011).…”