Bożena Leszczyńska-Gorzelak

T helper 1- and T helper 2-type cytokine imbalance in pregnant women with pre-eclampsia.

OBJECTIVES The purpose of our study was to investigate T helper 1/T helper 2 balance in pregnant women with pre-eclampsia. STUDY DESIGN 18 patients with pre-eclampsia and 20 healthy pregnant women were included in the study. Peripheral blood mononuclear cells (PBMC) were stimulated with phytohaemagglutinin (PHA) for 48 h. Cytokine: interleukin-2 (11-2), interferon-gamma (IFN-gamma) and interleukin-10 (I1-10) concentrations in culture supernatants were determined using the ELISA method. Statistical analysis was performed using a standard non-parametric Mann-Whitney U-test. RESULTS We found that in pre-eclamptic patients PHA-stimulated 11-2 and IFN-y production was significantly higher (P<0.001) and I1-10 production significantly lower (P<0.005) in comparison with the control group. CONCLUSION These results could suggest that there is Th1/Th2 imbalance in pre-eclamptic patients with predominant Th1-type immunity.

The predominance of Th17 lymphocytes and decreased number and function of Treg cells in preeclampsia.

The aim of this study was to estimate the prevalence of CD3(+)CD4(+) T lymphocytes producing IL-17, IL-2, IFN-γ, and IL-4, plus CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells, in peripheral blood of patients with preeclampsia and healthy women in the third trimester of normal pregnancy. Another purpose was to assess the immunosuppressive activity of Treg cells from patients with preeclampsia compared with controls. Thirty-four preeclampsia patients and 27 healthy pregnant women were included. The percentages of CD4(+)CD25(+)FoxP3(+) Treg cells and CD3(+)CD4(+) T lymphocytes with intracellular expressions of cytokines were estimated using monoclonal antibodies and flow cytometry. In vitro functional assays were performed using a Treg Cell Isolation Kit and (3)H-thymidine incorporation assays. The percentage of CD3(+)CD4(+) T lymphocytes producing IL-17A was significantly higher in preeclampsia than in healthy, normotensive pregnant women in the third trimester (p<0.001). The population of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower in the study group compared with controls (p<0.05). There was no change in the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes from preeclampsia patients without Treg cells and after addition of autologous Treg cells. In normal pregnancy, the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes was significantly higher without Treg cells compared with the response after addition of autologous Treg cells (p<0.05). The results suggest up-regulation of the Th17 immune response in preeclampsia. The decreased number and function of Treg cells may be responsible for activating the inflammatory response characteristic of this disorder. In preeclampsia, the predominance of Th17 immunity could act through modulating the Th1/Th2 immune balance.

The expressions of intracellular cytokines in the lymphocytes of preeclamptic patients

Darmochwal‐Kolarz D, Rolinski J, Leszczynska‐Gorzelak B, Oleszczuk J. The expressions of intracellular cytokines in the lymphocytes of preeclamptic patients. AJRI 2002; 48:381–386

Activated T lymphocytes in pre-eclampsia.

The aim of our study was to investigate the activation markets of T CD3+, T helper CD4+ and T cytotoxic CD8+ cells, as well as, the populations of T naïve CD4+ CD45RA+, T memory CD4+ CD45RO+ and T regulatory lymphocytes in PE and healthy pregnant women.

Glucocorticoids in Pregnancy

The fetus may be exposed to increased endogenous or synthetic glucocorticoid (GS) exposure in late gestation. Approximately 7% of pregnant women in Europe and North America are treated with synthetic GSs to promote lung maturation in fetuses at risk of preterm delivery. Maternal steroid treatment before preterm delivery is one of the best documented and most cost effective life saving treatments in prenatal medicine but, in certain circumstances, the price of accelerated lung maturity may be loss of brain cells, increased neurodevelopmental disability, intra-uterine growth restriction (IUGR), and an increased risk of preterm delivery, of programming of post-natal hypertension, and of increased post-natal activity in the hypothalamo-pituitary-adrenal (HPA) axis. Placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is the key enzyme which protects the fetus from overexposure to GSs by their oxidation into inactive derivates. We review the evidence for the metabolism of GSs during pregnancy and how endogenous and synthetic GSs cause other changes in the placenta which affect fetal development.

Comparative analysis of the maternal and umbilical interleukin-8 levels in normal pregnancies and in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation.

Objectives. The aim of this study was to determine the maternal and umbilical cord serum levels of interleukin-8 (IL-8) in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation (IUGR), and in normotensive pregnancies. Patients and methods. The study was carried out on 15 patients with singleton pregnancies complicated by preeclampsia with appropriate for gestational age weight infants and 12 pregnant patients with preeclampsia complicated by IUGR. The control group consisted of 10 healthy normotensive delivering patients with singleton uncomplicated pregnancies. Maternal and umbilical serum IL-8 concentrations were estimated using the ELISA method. Results. There were no statistically significant differences in patient profiles between the groups. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study groups in comparison with the control group. Lower birth weight and lower gestational age at birth were observed in the group of patients with preeclampsia complicated by IUGR. Increased maternal and umbilical serum levels of IL-8 were found in both preeclamptic patient groups in comparison with the control group. The umbilical cord blood concentrations of IL-8 in all groups of patients tended to be higher in comparison with the maternal blood. Conclusions. It seems that these higher IL-8 concentrations may be associated with apoptosis, inflammation, neutrophil activation, endothelial cell damage and dysfunction, and increased endothelial permeability. They may also participate in an attempt to compensate for the imbalanced apoptosis and vascular resistance. Our findings suggest a possible significant role of IL-8 in the pathogenesis and sequelae of preeclampsia, especially in preeclamptic pregnancies complicated by IUGR.

Evaluation of maternal and umbilical serum TNFα levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus

Objective. The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFα serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients. Patients and methods. The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFα concentrations were estimated using a sandwich ELISA assay. Results and conclusions. Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFα levels than those in the normotensive controls. Our findings and other reports indicate that TNFα may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor α (TNFα) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental–fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.

Pregnancy in Women with Epilepsy

The aim of this study was to analyze the outcome of pregnancy and delivery in epileptic women. A retrospective review of the 41 pregnant women with epilepsy who delivered in the Department of Obstetrics and Perinatology of the University School of Medicine in Lublin over 7 years (1993–1999) was carried out. Women with epilepsy had more pregnancy complications including premature labor, anemia, hypertension, vaginal bleeding, urinary tract infection, nausea and vomiting. An increased risk of congenital malformations and intrauterine fetal growth retardation was observed. Women with epilepsy require more extensive pregnancy planning including neurologic and preconceptional care.

Nitric oxide for treatment of threatened preterm labor.

Objective: The aim of our study was the assessment of effectiveness of nitroglycerin as a donor of nitric oxide, administered in the form of transdermal therapeutic system, applied in the treatment of threatening preterm labor. Patients and methods: The study was carried out on 30 pregnant patients with the symptoms of threatening preterm labor between 27th and 34th week of gestation. The patients were given nitroglycerin in the form of transdermal system releasing 5 mg of nitroglycerin in 24 h. Results: In our study the decrease in contractility and relaxation of uterus was observed in all obstetric patients. No changes in the fetal pulse rate and cardiotocographic tracing in the course of treatment and after completing treatment were observed. Conclusion: Nitroglycerin in the form of transdermal therapeutic system releasing nitric oxide may be an effective and safe tocolytic drug, however, further investigation needs to be performed.

Blood myeloid and lymphoid dendritic cells are stable during the menstrual cycle but deficient during mid-gestation

The aim of this study was to estimate the populations of peripheral blood myeloid and lymphoid dendritic cells (CD1c(+), BDCA-2(+), BDCA-4(+)) and the CD1c(+):BDCA-2(+) ratio in phases of the ovarian cycle and in normal pregnant patients. 18 non-pregnant women and 17 normal pregnant women were included. Dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies (mAbs) against blood dendritic cell antigens (anti-BDCA-1, BDCA-2, BDCA-4) and estimated using flow cytometry. CD1c(+), BDCA-2(+) and BDCA-4(+) dendritic cells were present in the follicular and luteal phases of the ovarian cycle and in all trimesters of normal pregnancy. The percentages of CD1c(+) dendritic cells did not differ between the follicular and luteal phases of the ovarian cycle. The percentage of BDCA-2(+) dendritic cells was lower in the luteal phase of the ovarian cycle compared with the follicular phase, but the differences were not statistically significant. The CD1c(+):BDCA-2(+) cell ratio was significantly lower in the luteal phase compared with the follicular phase of the ovarian cycle. The numbers of dendritic cells were significantly lower in the second trimester when compared with the first and third trimesters of normal pregnancy. Furthermore, in the second trimester, the CD1c(+):BDCA-2(+) ratio was higher than in the other trimesters of normal pregnancy. All populations of dendritic cells and the CD1c(+):BDCA-2(+) ratio did not differ in the first and third trimesters of physiological pregnancy. Our results suggest that myeloid and lymphoid dendritic cells are not affected by steroid hormones during the menstrual cycle. The deficiency of peripheral blood dendritic cells observed during the second trimester of normal pregnancy can be associated with their migration to the uterus during the second physiological invasion by cytotrophoblast.