Chemokines and Leukocyte Activation in the Fetal Circulation During Preeclampsia (original) (raw)
Related papers
2010
Background: Preeclampsia is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response with activation of both the innate and adaptive arms of the immune system. Cytokines, chemokines and adhesion molecules are central to innate and adaptive immune processes. The purpose of this study was to determine circulating levels of cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia in a comprehensive manner, and to investigate their relationship to the clinical features and laboratory parameters of the study participants, including markers of overall inflammation (C-reactive protein), endothelial activation (von Willebrand factor antigen) and endothelial injury (fibronectin), oxidative stress (malondialdehyde) and trophoblast debris (cell-free fetal DNA). Results: Serum levels of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, interferon-gamma-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were measured in 60 preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women by multiplex suspension array and ELISA. In normal pregnancy, the relative abundance of circulating IL-18 over IL-12p70 and the relative deficiency of the bioactive IL-12p70 in relation to IL-12p40 might favour Th2-type immunity. Although decreased IL-1ra, TNF-alpha and MCP-1 concentrations of healthy pregnant relative to non-pregnant women reflect anti-inflammatory changes in circulating cytokine profile, their decreased serum IL-10 and increased IP-10 levels might drive pro-inflammatory responses. In addition to a shift towards Th1-type immunity (expressed by the increased IL-2/IL-4 and IFN-gamma/ IL-4 ratios), circulating levels of the pro-inflammatory cytokines IL-6 and TNF-alpha, the chemokines IL-8, IP-10 and MCP-1, as well as the adhesion molecules ICAM-1 and VCAM-1, were raised in preeclampsia compared with healthy pregnancy, resulting in an overall pro-inflammatory systemic environment. Increased IP-10, MCP-1, ICAM-1 and VCAM-1 concentrations of preeclamptic patients showed significant correlations with blood pressure values, renal and liver function parameters, as well as with CRP, malondialdehyde, von Willebrand factor antigen and fibronectin levels.
Activation of Leukocytes During the Uteroplacental Passage in Preeclampsia
Hypertension, 2002
Endothelial dysfunction and inflammation appear to play a major role in the pathogenesis of preeclampsia. We hypothesize that a chronic inflammation in the decidua and placenta during preeclampsia may lead to a local leukocyte activation in this compartment. Venous blood was sampled simultaneously from antecubital and uterine veins during cesarean sections in 30 women with preeclampsia, 29 with uncomplicated pregnancies, and from 17 nonpregnant women. The expression of adhesion molecules and complement-related markers on neutrophils and monocytes was analyzed by flow cytometry. In patients with preeclampsia, neutrophil expression of the integrins CD11a, CD11b, and CD11c and of the complement related markers CD35 and CD59 was significantly higher in samples from uterine than from antecubital veins . No differences were found in nonpregnant women. On monocytes the expression of the Sialyl Lewis x antigen, the integrins CD11a, CD11c, and CD49d, and the complement-related markers CD46 a...
Inflammatory disturbances in preeclampsia: Relationship between maternal and umbilical cord blood
Journal of Pregnancy, 2012
Preeclampsia (PE) is one of the main causes of maternal and fetal mortality and morbidity. PE is associated with an inflammatory state and with oxidative stress, in maternal circulation. Our aim was to evaluate and compare the levels of oxidative stress and inflammatory markers in maternal and umbilical cord blood (UCB), in normal and PE pregnancies. We measured acute-phase proteins (CRP and α1-antitrypsin), proinflammatory cytokines (IL-6 and TNF-α), leukocyte activation (elastase, lactoferrin, sLselectin, sVCAM, sPECAM), total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), and uric acid levels. We studied 42 healthy pregnant women, 46 PE women, and their neonates. The concentrations of IL-6, TNF-α, α1-antitrypsin, CRP, sVCAM, uric acid, and TBARS were significantly higher, and sL-selectin was significantly lower in PE pregnant women as compared with normotensive pregnant women. In newborns uric acid, α1-antitrypsin, and CRP values were significantly higher in PE; leukocyte count, sL-selectin, lactoferrin, and the ratio elastase/α1-antitrypsin were significantly lower. Our data suggest that PE pregnancy is associated with an enhanced maternal inflammatory condition, which is reflected in fetal circulation. This enhanced inflammatory state seems to be related to endothelial dysfunction and increased cytokine synthesis, rather than with neutrophil activation.
Evaluation of Leukocytes and Neutrophils, Markers of Inflammatory Syndrome in Preeclampsia
2010
Introduction: In pregnancies with preeclampsia, there is a generalized inflammatory response, which is much more intense than in normal pregnancy. Aim: To evaluate leukocytes and neutrophils in the serum of pregnant women with preeclampsia and to compare these values to normal pregnancy. To investigate a possible relation between the detected values and the severity of preeclamptic syndrome. Material and method: A transversal study was performed in three groups of patients: group 1 (preeclampsia), group 2 (normal pregnancy), group 3 (control). The samples were processed using a multichannel automated hematology analyzer-ACCOS 319. The results obtained were processed by descriptive and comparative statistical methods. Results: A significant increase in leukocyte and neutrophil values was found in preeclampsia compared to normal pregnancy. Also, for group 2 (PE), there was no correlation between the number of leukocytes, neutrophils, respectively, and SBP and uric acid values, but a significant correlation was found between the studied inflammatory markers and DBP values. Conclusions: Leukocyte and neutrophil values can be considered markers of the inflammatory syndrome present in preeclampsia. These parameters were positively correlated with DBP values.
Aspects of inflammation, angiogenesis and coagulation in preeclampsia
Preeclampsia is a major challenge to obstetricians, due to its impact on maternal and fetal morbidity and mortality and the lack of preventive and treatment strategies. The overall aim of this thesis is to increase the knowledge of the pathogenesis of preeclampsia including the role of inflammation, angiogenesis and coagulation, both locally at the fetomaternal interface and in the maternal circulation. Uncompensated maternal endothelial inflammatory responses to factors from stressed trophoblasts seem to be a major contributor to the syndrome, together with an imbalance in angiogenesis and an activated coagulation system. An increasing amount of data indicates an involvement of the immune system with defect tolerance to the conceptus as an integral part of the pathogenesis, at least in early-onset preeclampsia (EOP). We showed that a single administration of human preeclampsia serum in pregnant IL-10 −/− mice induced the full spectrum of preeclampsia-like symptoms including hypoxic injury in uteroplacental tissues and endotheliosis in maternal kidneys. Importantly, preeclampsia serum, as early as 12 to 14 weeks of gestation, disrupted cross talk between trophoblasts and endothelial cells in an in vitro model of endovascular activity (Tube formation test). These results indicate that preeclamptic sera can be used to better understand the pathophysiology and to predict the disorder. Preeclampsia has been associated with increased inflammation, aberrant angiogenesis and activated coagulation, but their correlation and relative contribution are unknown. We found that markers for all these mechanisms were independently associated with preeclampsia. Cytokines, chemokines, and complement factors seem all to be part of a Th1-associated inflammatory reaction in preeclampsia, more pronounced in EOP than in late-onset preeclampsia (LOP), in line with a more homogeneous pathogenesis in EOP as based on placental pathology. In women with intrauterine growth restriction (IUGR), with an anticipated pathologic placentation, only differences in levels for sFlt-1 and PlGF were found in comparison with mothers without IUGR. Thus, sFlt-1 and PlGF seem to be indicators of placental pathology, Results and discussion 4.1 Paper I 4.2 Paper II 4.3 Paper III 4.4 Paper IV 5 Summary and conclusions 6 Future perspectives 7 Acknowledgments 8 References 12
American Journal of Obstetrics and Gynecology, 1998
OBJECTIVE: Our purpose was to investigate circulating levels of vascular cell adhesion molecule-1 in the peripheral and uteroplacental circulations during normotensive and hypertensive pregnancies. STUDY DESIGN: This prospective observational study involved 2 patient groups. Group 1 consisted of 22 women with pre-eclampsia and 30 normotensive women followed up longitudinally through pregnancy and post partum. There were an additional 13 women with established gestational hypertension. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects undergoing cesarean delivery. Plasma levels of vascular cell adhesion molecule-1 were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. RESULTS: In group 1 vascular cell adhesion molecule-1 levels did not change significantly throughout normal pregnancy and post partum. Women with established pre-eclampsia had increased vascular cell adhesion molecule-1 levels compared with the normotensive pregnancy group (P = .01). Vascular cell adhesion molecule-1 levels were not elevated in women with established gestational hypertension. In group 2 significantly higher levels of vascular cell adhesion molecule-1 were detected in the uteroplacental (P < .0001) and peripheral (P < .0001) circulations of pre-eclamptic women by comparison with normotensive women. In the pre-eclamptic group there was a tendency toward higher vascular cell adhesion molecule-1 levels in the peripheral circulation than in the uteroplacental circulation (P = .06). In contrast to vascular cell adhesion molecule-1, circulating levels of E-selectin and intercellular adhesion molecule-1, other major leukocyte adhesion molecules expressed by the endothelium, were not different in pre-eclamptic and normotensive pregnancies. CONCLUSION: Established pre-eclampsia is characterized by selective dysregulation of vascular cell adhesion molecule-1 homeostasis. This event is not an early preclinical feature of pre-eclampsia, does not persist post partum, is not a feature of nonproteinuric gestational hypertension, and is not observed with other major leukocyte adhesion molecules. Induction of vascular cell adhesion molecule-1 expression in pre-eclampsia may contribute to leukocyte-mediated tissue injury in this condition or may reflect perturbation of other, previously unrecognized, functions of this molecule in pregnancy.
Vascular cell adhesion molecule-1 (VCAM-1) and leukocyte activation in pre-eclampsia and eclampsia
International Journal of Gynecology & Obstetrics, 1998
Objecti¨e: To evaluate the levels of VCAM-1 in pre-eclampsiareclampsia as a possible marker of leukocyte activation and endothelial damage. Methods: We performed a case-control study on 25 healthy pregnant women and 35 patients diagnosed as pre-eclampsia or eclampsia which were randomly selected. Peripheral venous blood samples Ž . were obtained and serum levels of VCAM-1 were measured by enzyme-linked immunoassay ELISA . Results: In pre-eclampsiareclampsia, VCAM-1 levels were higher than in normal pregnancy. Serum concentrations of VCAM-1 were significantly higher in severe pre-eclampsia and eclampsia compared to mild pre-eclampsia or healthy controls. ROC analysis detected that VCAM-1 G 450 ngrml had a sensitivity of 0.79 and a specificity of 0.90 in detecting severe pre-eclampsia and eclampsia. Conclusion: This is the first study to correlate VCAM-1 levels with severity of disease in pre-eclampsia. Our findings indicate that increasing levels of soluble VCAM-1 are present in the circulation of patients with severe pre-eclampsiareclampsia compared to mild pre-eclampsia or healthy pregnant women. Elevated VCAM-1 levels may represent a possible mechanism by which endothelial cells attract leukocytes and cause endothelial cell damage. ᮊ 1998 International Federation of Gynecology and Obstetrics International Federation of Gynecology and Obstetrics Ž . P I I S 0 0 2 0 -7 2 9 2 9 8 0 0 1 3 8 -6 ( ) E. Budak et al.