interleukin-8 and Fetal-Growth-Retardation

It is possible that in fetal growth restriction without pre-eclampsia endothelial cell activation does not occur. This might be either because there is no release of 'factor X' or because of maternal resistance to its effects. To test this hypothesis, we took blood samples from 26 women with pre-eclampsia (without fetal growth restriction), 13 women with fetal growth restriction (without pre-eclampsia) and 24 normal pregnant controls, and measured the circulating levels of three markers of endothelial cell activation (soluble VCAM, ICAM and E-selectin) and three cytokines [tumour necrosis factor-a (TNF-alpha), interleukin-6 (IL-6) and -8 (IL-8)]. The levels of the markers of endothelial cell activation were raised in both pre-eclampsia and fetal growth restriction pregnancies compared with controls; however, the levels of TNF-alpha, IL-6 and IL-8 were significantly raised in pregnancies complicated by pre-eclampsia, but not in fetal growth restriction, compared with controls. These data show that endothelial cell activation is common to both pre-eclampsia and fetal growth restriction, but that the circulating levels of cytokines are elevated only in pre-eclampsia. Thus, it seems likely that endothelial cell activation is a consequence of a failure of trophoblast invasion and that a further step is required, possibly involving cytokine release, for the expression of the full clinical picture of pre-eclampsia.

Topics: Adult; Blood Pressure; Body Mass Index; E-Selectin; Endothelium; Enzyme-Linked Immunosorbent Assay; Female; Fetal Growth Retardation; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Pilot Projects; Pre-Eclampsia; Pregnancy; RNA, Messenger; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Fetal growth restriction (FGR) and pre-eclampsia with fetal growth restriction (PE/FGR) are high-risk perinatal diseases that may involve high levels of human chorionic gonadotropin (hCG) and mitochondrial dysfunction. However, little is known about how these factors affect placental function. We investigated how mitochondrial dysfunction and high hCG expression affected placental function in unexplained FGR and PE/FGR. We observed elevated expression of hCGβ and growth differentiation factor 15 mRNA and protein levels in the placenta with both diseases. Likewise, antiangiogenic factors, such as Ang2, IP10, sFlt1, IL8, IL1B, and TNFα, were also upregulated at the mRNA level. In addition, the expression of COXI and COXII which encoded by mitochondrial DNA were significantly decreased in both diseases, suggesting that mitochondrial translation was impaired. Treatment with hCG increased Ang2, IP10, IL8, and TNFα mRNA levels in a dose-dependent manner via the p38 and JNK pathways. Mitochondrial translation inhibitors increased hCGβ expression through stabilization of HIF1α, and increased IL8 and TNFα mRNA expression. These results revealed that high expression of hCG due to mitochondrial translational dysfunction plays an important role in the pathogenesis of FGR and PE/FGR.

Topics: Chemokine CXCL10; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Fetal Growth Retardation; Humans; Interleukin-8; Mitochondria; Placenta; Pre-Eclampsia; Pregnancy; RNA, Messenger; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor Receptor-1

We investigated the association between maternal zinc level during pregnancy and the risks of low birth weight (LBW) and small for gestational age (SGA) infants in a large population-based birth cohort study. In this study, 3187 pregnant women were recruited. For serum zinc level, 2940 pregnant women were sufficient (≥56 μg/dL) and 247 deficient (<56 μg/dL). Of interest, 7.3% newborns were with LBW among subjects with low zinc level (RR: 3.48; 95% CI: 2.03, 5.96; P < 0.001). Adjusted RR for LBW was 3.41 (95% CI: 1.97, 5.91; P < 0.001) among subjects with low zinc level. Moreover, 15.0% newborns were with SGA among subjects with low zinc level (RR: 1.98; 95% CI: 1.36, 2.88; P < 0.001). Adjusted RR for SGA was 1.93 (95% CI: 1.32, 2.82; P < 0.001) among subjects with low zinc level. A nested case-control study within above cohort showed that maternal serum zinc level was lower in SGA cases as compared with controls. By contrast, maternal serum C-reactive protein, TNF-α and IL-8 levels were significantly higher in SGA cases than that of controls. Moreover, nuclear NF-κB p65 was significantly up-regulated in placentas of SGA cases as compared with controls. Taken together, maternal zinc deficiency during pregnancy elevates the risks of LBW and SGA infants.

Topics: Adult; C-Reactive Protein; Case-Control Studies; Cohort Studies; Female; Fetal Development; Fetal Growth Retardation; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Interleukin-8; Maternal-Fetal Exchange; Placenta; Pregnancy; Transcription Factor RelA; Tumor Necrosis Factor-alpha; Up-Regulation; Zinc

Aim of this study was to assess concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) in the serum of newborns with diagnosed intrauterine growth restriction (IUGR) in comparison to concentrations in serum of newborns with weight appropriate for gestational age (AGA).. Research was conducted at the Lodz Medical University Clinic of Neonatology during 2010-2011. Surveyed group consisted of 50 hypotrophic full-term infants of single pregnancies (average weight: 2329 ± 287 g); control group, enclosing 50 infants AGA (average weight: 3544 ± 2161 g). Both groups received average Apgar score of 9 points. Concentrations of analysed cytokines were marked between 4-6 hours after birth. The enzyme-linked immunosorbent assay (ELISA) test was used to determine interleukins concentrations. Study was prospective. Statistics on the data were conducted with the Kolmogorov-Smirnov test. Significance level: p < 0.05.. Concentrations of IL-6 and IL-18 were elevated in the IUGR group in a statistically significant manner in comparison to the control group.. An elevated level of IL-6 and IL-18 in the IUGR group, comparing to control group, signifies the existence of inflammation in the process of developing IUGR, therefore, screening tests estimating levels of interleukins as IL-6 and IL-18 might be clinically useful in predicting the occurrence of IUGR and help preventing it.

Topics: Apgar Score; Case-Control Studies; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Infant, Small for Gestational Age; Interleukin-18; Interleukin-6; Interleukin-8; Pregnancy; Pregnancy Complications, Infectious; Term Birth

Recurrent pregnancy loss (RPL) occurs in ∼5% of women. However, the etiology is still poorly understood. Defects in decidualization of the endometrium during early pregnancy contribute to several pregnancy complications, such as pre-eclampsia and intrauterine growth restriction (IUGR), and are believed to be important in the pathogenesis of idiopathic RPL. We performed microarray analysis to identify gene expression alterations in the deciduas of idiopathic RPL patients. Control patients had one antecedent term delivery, but were undergoing dilation and curettage for current aneuploid miscarriage. Gene expression differences were evaluated using both pathway and gene ontology (GO) analysis. Selected genes were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A total of 155 genes were found to be significantly dysregulated in the deciduas of RPL patients (>2-fold change, P < 0.05), with 22 genes up-regulated and 133 genes down-regulated. GO analysis linked a large percentage of genes to discrete biological functions, including immune response (23%), cell signaling (18%) and cell invasion (17.1%), and pathway analysis revealed consistent changes in both the interleukin 1 (IL-1) and IL-8 pathways. All genes in the IL-8 pathway were up-regulated while genes in the IL-1 pathway were down-regulated. Although both pathways can promote inflammation, IL-1 pathway activity is important for normal implantation. Additionally, genes known to be critical for degradation of the extracellular matrix, including matrix metalloproteinase 26 and serine peptidase inhibitor Kazal-type 1, were also highly up-regulated. In this first microarray approach to decidual gene expression in RPL patients, our data suggest that dysregulation of genes associated with cell invasion and immunity may contribute significantly to idiopathic recurrent miscarriage.

Topics: Abortion, Habitual; Adult; Cell Movement; Decidua; Down-Regulation; Embryo Implantation; Endometrium; Female; Fetal Growth Retardation; Gene Expression Profiling; Gene Expression Regulation, Developmental; Humans; Inflammation; Interleukin-1; Interleukin-8; Matrix Metalloproteinases; Middle Aged; Oligonucleotide Array Sequence Analysis; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Proteinase Inhibitory Proteins, Secretory; Up-Regulation

While elevated levels of proinflammatory cytokines are clearly associated with preterm birth, the relation between cytokines and fetal growth is unclear. The authors examined associations between umbilical cord serum cytokine concentrations and risk of small-for-gestational-age (SGA) and preterm birth. This cross-sectional analysis was nested within a National Institute of Child Health and Human Development-University of Alabama population-based cohort study of high-risk prenatal care patients in Jefferson County, Alabama. Patients were enrolled between 1985 and 1988. For 370 singletons, umbilical cord serum concentrations of interferon gamma (IFN-gamma), tumor necrosis factor alpha, and interleukins 12p70, 4, and 10 were determined. Associations between each cytokine and SGA and preterm delivery were evaluated using log binomial regression. Increasing log concentration of tumor necrosis factor alpha was associated with an increased risk of preterm birth (risk ratio (RR) = 2.00, 95% confidence interval (CI): 1.31, 3.06). IFN-gamma was associated with a decreased risk of SGA birth (RR = 0.78, 95% CI: 0.61, 1.01). After stratification for preterm birth status, the association between IFN-gamma concentration and SGA birth was pronounced among preterm babies (RR = 0.56, 95% CI: 0.31, 1.01). The observations regarding IFN-gamma, which is involved in the activation of adaptive immune responses and regulation of trophoblast function, suggest that IFN-gamma levels at birth may be related to fetal growth restriction.

Topics: Adult; Alabama; Cross-Sectional Studies; Cytokines; Female; Fetal Blood; Fetal Growth Retardation; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infant, Newborn; Infant, Small for Gestational Age; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-4; Interleukin-6; Interleukin-8; Linear Models; Pregnancy; Pregnancy Outcome; Pregnancy, High-Risk; Premature Birth; Prospective Studies; Risk Factors; Tumor Necrosis Factor-alpha

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.. 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.. 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.. 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.

Topics: Adult; Birth Weight; Case-Control Studies; Female; Fetal Blood; Fetal Growth Retardation; Gestational Age; Humans; Infant, Newborn; Interleukin-8; Pre-Eclampsia; Pregnancy

Preeclampsia is a common and major cause of maternal and perinatal morbidity and mortality. Human leucocyte antigen (HLA) susceptibility and impaired adaptation of the T lymphocyte sub-population and a bi-directional effect of T helper cytokines on the outcome of pregnancy have been reported in patients with preeclampsia. The association between maternal HLA class II and T helper cytokines in women with preeclampsia was investigated in seventy-six preeclamptic women and normotensive controls using Terasaki microlymphocytotoxicity test. T helper cytokines interleukin (IL)-8, IL-6, IL-4, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma were estimated in the maternal blood and placenta by enzyme-linked immunosorbent assay (ELISA). Histopathological evaluation of the placenta was also carried out. HLA class II DR2, DR4, DR5, DRw8, DRw10, DRw11, DRw18, and DQw2 had significant relative risk ratios for preeclampsia, while DQw3 was more common in the controls. DR4-DRw11-DQw2 haplotype was more common in preeclamptic women with intrauterine growth restriction, low birth weight and placental weight, increased expression of T helper cytokines IL-8, TNF-alpha and IFN-gamma and abnormal uteroplacental vasculature. These findings suggest that HLA class II DR4-DRw11 -DQw2 haplotypes may be associated with preeclampsia with intrauterine growth restriction through low placental weight from impaired placental development, as a result of increased expression of T helper 1 cytokines IL-8, TNF-alpha and IFN-gamma.

Topics: Adult; Birth Weight; Case-Control Studies; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Fetal Growth Retardation; Histocompatibility Antigens Class II; HLA Antigens; Humans; Interferon-gamma; Interleukin-4; Interleukin-6; Interleukin-8; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Tumor Necrosis Factor-alpha

Our purpose was to investigate the participation of cytokines and neutrophils in fetal distress.. Umbilical cord serum interleukin-6 (IL-6), interleukin-8 (IL-8), and plasma granulocyte elastase (GEL) were measured in 30 normally grown newborns without fetal distress (Group A), 10 growth-retarded newborns without acute fetal distress (Group B), 5 normally grown newborns with fetal distress (Group C), and 5 growth-retarded newborns with fetal distress (Group D). Umbilical arterial blood pH and PO2 were also measured.. Umbilical arterial blood pH and PO2 in either Group C or Group D were significantly lower than those in either Group A or Group B. The concentration of IL-6 in Group D was significantly higher than that in either Group A, B, or C. The level of IL-8 in either Group C or Group D was significantly higher than that in either Group A or Group B. The concentrations of GEL in Group D was significantly higher than that in either Group A or Group B.. This study suggests that fetal distress in utero causes an elevation of immune factors such as IL-6, IL-8 and GEL.

Topics: Acidosis; Fetal Blood; Fetal Distress; Fetal Growth Retardation; Fetal Hypoxia; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Leukocyte Elastase

A large array of cytokines show high activity in amniotic fluid. Attempts have been made to quantify the concentrations or to track rising levels for diagnostic purposes when examining disturbances of the feto-maternal unit. However, the kinetics of cytokine production in the amniotic fluid are not well understood, and there is lack of knowledge about concomitant levels in fetal and maternal blood.. The presence of cytokines in fetal and placental cells was demonstrated by immunohistochemistry using mAb. Cytokines were quantified by enzymimmunoassay in amniotic fluid and fetal and maternal blood. This was done with regard to two disease states that quite frequently complicate the course of pregnancy, namely chorioamnionitis and intrauterine growth retardation. The cytokines examined were G-CSF, GM-CSF, TNF-alpha, IL-1, IL-6, and IL-8.. In chorioamnionitis, all cytokines, except GM-CSF, were elevated about 100 times in the amniotic fluid. An accompanying increase in maternal and fetal blood was only found for IL-6 and G-CSF; IL-8 was elevated in fetal blood only. Intrauterine growth retardation was characterized by elevated levels of TNF-alpha in the amniotic fluid, whereas G-CSF, GM-CSF, and IL-1 beta were significantly reduced. Immunohistochemistry showed that under normal conditions the cytokines are to be found in a characteristic distribution in certain cell types in the fetus, the placenta, and the placental bed. With rising concentrations, more cells seemed to be recruited for cytokine production, especially macrophages and decidual cells. In chorioamnionitis, fetal extramedullary granulopoiesis was augmented, and in intrauterine growth retardation, erythropoiesis as well as granulopoiesis were depressed.. Not only inflammatory disease but also intrauterine growth retardation is characterized by a changing cytokine pattern. Alterations in fetal hematopoiesis observed at postmortem examination of perinatal deaths can be correlated to changes in cytokine production within the feto-maternal unit.

Topics: Amniotic Fluid; Chorioamnionitis; Cytokines; Embryonic and Fetal Development; Enzyme-Linked Immunosorbent Assay; Female; Fetal Growth Retardation; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunohistochemistry; Interleukin-6; Interleukin-8; Placenta; Pre-Eclampsia; Pregnancy; Tumor Necrosis Factor-alpha

Concentrations of five cytokines, GM-CSF, G-CSF, IL-1, IL-6 and IL-8, were determined within five compartments under four different conditions: at the time of a Caesarean section performed between 25 and 38 weeks' gestational age in normal pregnancy without uterine contraction (n = 12), in normal pregnancy with labour already established (n = 8), in pregnancy complicated by amniotic infection (n = 11), or under the conditions of preeclampsia with fetal intrauterine dystrophy (n = 13), cytokine concentrations were determined in fetal arterial and venous blood, in amniotic fluid, and in retroplacentally obtained maternal blood and peripheral maternal blood. With dystrophy, the concentrations of GM-CSF, G-CSF and IL-1 were about 20-50% lower (P < 0.01) in the amniotic fluid, and IL-6 and IL-8 were elevated in maternal peripheral blood (P < 0.01) but not within maternal retroplacental blood. Thus, preeclampsia/intrauterine dystrophy is characterized by reduction of some cytokines within the amniotic fluid compartment and concomitant reactive augmentations of other cytokines within the maternal and fetal organism. With amniotic fluid infection, concentrations of G-CSF, IL-6 and IL-8 were elevated in all compartments (P < 0.001) but GM-CSF and IL-1 showed a significant rise only within amniotic fluid and retroplacental maternal blood (P < 0.001), a rise that was apparently not transmitted to peripheral maternal or fetal blood. Care was taken to exclude the presence of uterine contractions in the group of controls, because this condition by itself causes severe elevation of cytokine concentrations, which are pronounced within amniotic fluid.

Topics: Amniotic Fluid; Chorioamnionitis; Cytokines; Female; Fetal Blood; Fetal Growth Retardation; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Labor, Obstetric; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications