by In parallel, in vitro in a dually perfused placental cotyledon, most of placental TNF-alpha was released to the maternal side confirming the importance of placentally produced inflammatory mediators in the induction of the maternal systemic changes [34]. was observed in TNF-alpha before and after delivery in both groups. No difference was noticed in IL-6 levels in women of normotensive group long after delivery compared to that before delivery. Long after delivery IL-6 levels were statistically significant higher in preeclamptic women compared to normal controls (3.53 0.52 pg/ml versus 1.69 0.48 pg/ml,P: .02).Conclusion. Preeclamptic women remain under a status of increased inflammatory stress up to 12-14 weeks postpartum despite the fact that all the other signs of preeclampsia are resolved. == 1. Introduction == AT7519 Although there is no systemic inflammation during pregnancy, circulating cytokines AT7519 are found to be elevated in maternal plasma [1]. More specifically, normal pregnancy is characterized by local inflammatory response which leads to local production of proinflammatory cytokines that could be found in the systematic circulation. The presence of such cytokines in the systematic circulation might secondarily lead to subclinical systemic inflammatory response. In preeclampsia, a similar but exaggerated response occurs [2]. Preeclampsia is a severe pregnancy-specific disorder with an incidence which has been reported to be approximately 58% [3]. It is a syndrome defined by hypertension and proteinuria that also may be associated with myriad other signs and symptoms and often with subnormal fetal growth [4,5]. The mechanisms responsible for the pathogenesis of preeclampsia have not yet been clearly identified, but reduced uterine perfusion and placental ischemia are an important initiating event in this disorder, and inflammatory cytokines are thought to link placental ischemia with cardiovascular and renal dysfunction symptoms seen in this disorder [6]. Maternal serum levels of IL-6 and TNF-alpha play a significant role in pathogenesis of preeclampsia [7]. TNF-alpha is produced by monocytes, induces apoptosis, and inhibits proliferation of trophoblast cells in preeclampsia [8]. The fact that higher circulating levels of TNF-alpha were observed in preeclampsia than in gestational hypertension suggests an association with PKX1 disease severity [9]. Moreover, significantly increased soluble TNF-alpha receptors are found in the plasma of patients with preeclampsia [10]. Soluble TNF-alpha receptors bind with circulating TNF-alpha leading to a decrease of the ligand’s availability [10]. At least two different views on the role of soluble receptors of TNF-a in systemic circulation have AT7519 been expressed in the literature: (a) increased levels of TNF-soluble receptors in systemic AT7519 circulation may indicate either increased expression of the receptors on the cells’ surface, and therefore the increased sensitivity and responsiveness of these cells to elevated levels of TNF-a, as it has been shown in the preeclamptic women of our study or increased presence of systemic circulation proteases of the extracellular part of transmembrane TNF-receptor and (b) the presence of TNF-soluble receptor in the systemic circulation which does not document their ability to bind TNF-in systemic circulation, as the decay of the proteases is likely to affect the binding capacity. Furthermore, the poorly perfused and hypoxic placenta is thought to synthesize increased vasoactive factors, for example, soluble fms-like tyrosine kinase-1, cytokines (TNF-alpha, IL-6), and angiotensin II type 1 receptor antibodies) [11]. Such elevations could lead to endothelial dysfunction by decreasing bioavailable nitric oxide and increasing reactive oxygen species and endothelin-1 which in turn leads to altered renal function, decreased renal pressure natriuresis, increased total peripheral resistance, and hypertension [11,12]. Ischemic placenta leads to endothelial cell activation/dysfunction and enhances TNF-alpha synthesis which leads to induced structural and functional alterations in endothelial cells leading to preeclampsia via transcriptional regulation of the endothelin-1 gene by TNF-alpha [1317]. Conflicting results, however, are found regarding the role of circulating IL-6 and TNF-alpha in a review of the current literature. Many authors believe that circulating levels of TNF-alpha and IL-6 are enhanced in preeclamptic patients compared with normotensive and nonpregnant women [18]. On the contrary, others did not manage to identify a correlation between maternal serum levels of IL-6 or TNF-alpha and preeclampsia [19,20]. Furthermore, there is no information about maternal blood concentrations of IL-6 and TNF-alpha in women with preeclampsia long time after delivery. In the present study, we have evaluated maternal TNF-alpha and IL-6 plasma levels in normotensive pregnant women as well as in women with preeclampsia. We have also examined whether AT7519 the temporal changes in plasma TNF-alpha and IL-6 levels from the antepartum to the postpartum period correlate with the regression of preeclampsia. == 2. Materials and Methods == Two groups of patients were studied: normal controls and women with preeclampsia. The preeclamptic group consisted of 17 normotensive women who later in their pregnancy developed preeclampsia. The diagnosis of preeclampsia was established according to the criteria developed by the National High Blood Pressure Education Programme Working Group [21]: systolic blood pressure of more than 140 mm Hg, diastolic pressure higher than 90 mm.
