interleukin-8 and Fetal-Membranes--Premature-Rupture

Topics: Collagen; Female; Fetal Membranes, Premature Rupture; Glycoproteins; Humans; Interleukin-8; Leukocyte Elastase; Obstetric Labor, Premature; Pregnancy

We investigated whether cervical shortening and high interleukin (IL)-8 in cervical mucus were valuable indications for treatment to prevent premature birth and preterm, pre-labor rupture of membranes (pPROM).. Pregnant women were divided into group A, in which neither cervical IL-8 nor cervical length was measured in the middle trimester; and groups B and C, in which cervical length and cervical IL-8 were measured, and bed rest or cerclage was performed when cervical shortening was detected. In group B, vaginal washing with povidone iodine and insertion of chloramphenicol vaginal tablets were carried out in women with IL-8 elevations.. In group B, duration of pregnancy was significantly prolonged compared with group A and C, and occurrence of pPROM was significantly lower. No significant differences were found in those rates between groups A and C.. Successful treatment for women with IL-8 elevations in cervical mucus decreased rates of premature birth or pPROM.

Topics: Cervix Mucus; Chloramphenicol; Disease Susceptibility; Female; Fetal Membranes, Premature Rupture; Humans; Interleukin-8; Obstetric Labor, Premature; Pregnancy; Pregnancy Outcome; Prospective Studies; Treatment Outcome

This study was performed to correlate cervicovaginal fluid and umbilical cord plasma level of IL-6 and IL-8 in patients with premature rupture of the membranes (PROM) and to see the effect of antibiotics on those concentrations. As a part of a randomized controlled trial of treatment in PROM with antibiotics, cervicovaginal fluid was sampled before delivery for measurement of IL-6 and IL-8 and for bacteria from 36 patients less than 36 weeks of gestation. Umbilical cord plasma was also collected. Concentrations of IL-6 and IL-8 were measured by an ELISA. Neonatal infections were noted in a total of 9 cases, including bacteria detection (Escherichia coli 2 cases, GBS and Streptococcus constellata) in 4 cases. Correlation between IL-6 in cervicovaginal fluid and in cord plasma (r = 0.881, p < 0.0001) was stronger than that of IL-8 (r = 0.469, p < 0.01). The difference of concentrations in IL-6 and IL-8 was not significant between cases with (n = 20) and without (n = 16) ampicillin. Our observation indicates that the measurement of IL-6 concentrations in cervicovaginal fluid is a useful marker for PROM patients who are more likely to develop neonatal infection and the antibiotic treatment does not necessarily produce their beneficial effects on fetuses at the risk of infection.

Topics: Anti-Bacterial Agents; Bacterial Infections; Birth Weight; Body Fluids; Cervix Uteri; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Pregnancy; Prospective Studies; Vagina

In cases of premature rupture of membranes (PROM), an early detection of fetal infection is necessary in order to weigh infectious complications against prematurity. As routine parameters (leukocytes, C-reactive protein (CRP), fever, and fetal tachycardia) lack satisfactory sensitivity and specificity, this study evaluates whether the determination of interleukin-6 (IL-6), interleukin-8 (IL-8) or soluble interleukin-2 receptor (IL-2R) in maternal serum could supplement or replace routine inflammation parameters.. In this prospective study results of clinical and laboratory parameters were investigated with respect to neonatal infection in 71 patients with PROM. IL-6, IL-8 and IL-2R were determined by enzyme immunoassays.. Best specificity and sensitivity could be demonstrated for CRP and IL-6. Both elevation of CRP and IL-6 correlated significantly (p<0.01 and p<0.001, respectively) with the onset of neonatal infection. At a cutoff of 11 pg/ml, IL-6 reaches a sensitivity of 81% and a specificity of 76%; CRP a specificity of 76% (cutoff 1.2 mg/dl) and a sensitivity of 56%. In 4/16 (25%) cases developing neonatal infection, IL-6 increased earlier than CRP. IL-8 and IL-2R results showed a less significant correlation with fetal outcome.. Determination of IL-6 in maternal serum can significantly contribute to an earlier detection of fetal infection in patients with PROM.

Topics: Area Under Curve; Bacterial Infections; C-Reactive Protein; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Interleukin-6; Interleukin-8; Leukocytosis; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Prospective Studies; Receptors, Interleukin-2; ROC Curve; Sensitivity and Specificity; Time Factors

To investigate whether altered expression of various inflammation-, angiogenesis-, and extracellular matrix-related mediators in cervicovaginal fluid (CVF) could be independently associated with acute histological chorioamnionitis (HCA), microbial-associated HCA, and funisitis in women with preterm premature rupture of membranes (PPROM).. Clinical data of 102 consecutive singleton pregnant women with PPROM at 23+0 to 34+0 weeks were retrospectively analyzed. CVF samples were collected upon admission. Levels of APRIL, DKK-3, IGFBP-1/2, IL-6/8, lipocalin-2, M-CSF, MIP-1α, MMP-8/9, S100A8A9, TGFBI, TIMP-1, TNFR2, uPA, and VDBP were determined by ELISA. Placentas were histologically examined after birth.. Multivariate logistic regression analyses showed that: (1) elevated CVF levels of IL-8 and TNFR2 were independently associated with acute HCA; (2) elevated CVF levels of IL-6, IL-8, M-CSF, MMP-8, and TNFR2 were independently associated with microbial-associated HCA; and (3) elevated CVF IL-8 and MMP-8 levels were independently associated with funisitis when adjusted for gestational age. Areas under the curves of the aforementioned CVF biomarkers ranged within 0.61-0.77, thereby demonstrating poor to fair diagnostic capacity for these clinical endpoints. HCA risk significantly increased as the CVF levels of each inflammatory mediator increased (P for trend < 0.05).. Herein, we identified several inflammatory biomarkers (IL-6/8, M-CSF, MMP-8, and TNFR2) in the CVF that are independently associated with acute HCA, microbial-associated HCA, and funisitis in women with PPROM. Furthermore, the degree of inflammatory response in the CVF, based on the levels of these proteins, demonstrated a direct relationship with HCA risk (especially risk severity).

Topics: Amniotic Fluid; Biomarkers; Chorioamnionitis; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Macrophage Colony-Stimulating Factor; Matrix Metalloproteinase 8; Pregnancy; Receptors, Tumor Necrosis Factor, Type II; Retrospective Studies

We sought to identify novel biomarkers in the amniotic fluid (AF) related to imminent spontaneous preterm delivery (SPTD) (≤ 14 days after sampling) in women with early preterm premature rupture of membranes (PPROM), using a protein microarray.. This was a retrospective cohort study of a total of 88 singleton pregnant women with PPROM (23+0 to 30+6 weeks) who underwent amniocentesis. A nested case-control study for biomarker discovery was conducted using pooled AF samples from controls (non-imminent delivery, n = 15) and cases (imminent SPTD, n = 15), which were analyzed using an antibody microarray. Quantitative validation of four candidate proteins was performed, using ELISA, in the total cohort (n = 88). IL-8, MMP-9, and Fas levels were additionally measured for the comparison and to examine association of SPTD with the etiologic factors of PPROM.. Of all the proteins studied in the protein microarray, four showed significant intergroup differences. Analyses of the total cohort by ELISA confirmed the significantly elevated concentrations of AF lipocalin-2, MMP-9, and S100 A8/A9, but not of endostatin and Fas, in women who delivered within 14 days of sampling. For inflammatory proteins showing a significant association, the odds of SPTD within 14 days increased significantly with an increase in baseline AF levels of the proteins (P for trend <0.05 for each) in each quartile, especially in the 3rd and 4th quartile.. We identified several potential novel biomarkers (i.e., lipocalin-2, MMP-9, and S100 A8/A9) related to SPTD within 14 days of sampling, all of which are inflammation-related molecules. Furthermore, the SPTD risk increased with increasing quartiles of each of these inflammatory proteins, especially the 3rd and 4th quartile of each protein. The present findings may highlight the importance of inflammatory mechanisms and the degree of activated inflammatory response in developing SPTD in early PPROM.

Topics: Adult; Amniotic Fluid; Biomarkers; Case-Control Studies; fas Receptor; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Interleukin-8; Matrix Metalloproteinase 9; Obstetric Labor, Premature; Pregnancy; Premature Birth; Protein Array Analysis; Retrospective Studies

Does proviral integration site for Moloney murine leukaemic virus (PIM)1 kinase play a role in regulating the inflammatory processes of human labour and delivery?. PIM1 kinase plays a critical role in foetal membranes in regulating pro-inflammatory and pro-labour mediators.. Infection and inflammation have strong causal links to preterm delivery by stimulating pro-inflammatory cytokines and collagen degrading enzymes, which can lead to rupture of membranes. PIM1 has been shown to have a role in immune regulation and inflammation in non-gestational tissues; however, its role has not been explored in the field of human labour.. PIM1 expression was analysed in myometrium and/or foetal membranes obtained at term and preterm (n = 8-9 patients per group). Foetal membranes, freshly isolated amnion cells and primary myometrial cells were used to investigate the effect of PIM1 inhibition on pro-labour mediators (n = 5 patients per treatment group).. Foetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and from preterm pre-labour rupture of membranes (PPROM) (n = 9 per group). Amnion was collected from women with and without preterm chorioamnionitis (n = 8 per group). Expression of PIM1 kinase was determined by qRT-PCR and western blotting. To determine the effect of PIM1 kinase inhibition on the expression of pro-inflammatory and pro-labour mediators induced by bacterial products lipopolysaccharide (LPS) (10 μg/ml) and flagellin (1 μg/ml) and pro-inflammatory cytokine tumour necrosis factor (TNF) (10 ng/ml), chemical inhibitors SMI-4a (20 μM) and AZD1208 (50 μM) were used in foetal membrane explants and siRNA against PIM1 was used in primary amnion cells. Statistical significance was set at P < 0.05.. PIM1 expression was significantly increased in foetal membranes after spontaneous term labour compared to no labour at term and in amnion with preterm chorioamnionitis compared to preterm with no chorioamnionitis. There was no change in PIM1 expression with preterm labour or PPROM compared to preterm with no labour or PPROM. In human foetal membranes, PIM1 inhibitors SMI-4a and AZD1208 significantly decreased the expression of pro-inflammatory cytokine interleukin-6 (IL6) and chemokines CXCL8 and CCL2 mRNA and release, prostaglandin prostaglandin F2α (PGF2α) release, adhesion molecule intercellular adhesion molecule 1 mRNA expression and release, and oxidative stress marker 8-isoprostane release after stimulation with either LPS or flagellin. Primary amnion cells transfected with PIM1 siRNA also showed decreased expression of IL6, CXCL8 and CCL2, PTGS2 mRNA and PGF2α release, and matrix metalloproteinase-9 (MMP9) expression, when stimulated with TNF.. None.. The conclusions were drawn from in vitro experiments using foetal membrane explants and primary cells isolated from amnion. Animal models are necessary to determine whether PIM1 kinase inhibitors can prevent spontaneous preterm birth in vivo.. PIM1 kinase inhibitors may provide a novel therapeutic approach for preventing spontaneous preterm birth.. Associate Professor Martha Lappas is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; grant no. 1047025). Funding for this study was provided by the NHMRC (grant no. 1058786), Norman Beischer Medical Research Foundation and the Mercy Research Foundation. The authors have no conflict of interest.

Topics: Benzylidene Compounds; Biphenyl Compounds; Chemokine CCL2; Chorioamnionitis; Cyclooxygenase 2; Extraembryonic Membranes; Female; Fetal Membranes, Premature Rupture; Flagellin; Gene Expression Regulation; Humans; Interleukin-6; Interleukin-8; Labor, Obstetric; Lipopolysaccharides; Matrix Metalloproteinase 9; Myometrium; Obstetric Labor, Premature; Pregnancy; Proto-Oncogene Proteins c-pim-1; RNA, Small Interfering; Thiazolidinediones; Thiazolidines; Tissue Culture Techniques; Tumor Necrosis Factor-alpha

Cervical length measurement has been uggested as a useful tool for predicting intra-amniotic infection/inflammation in preterm labor, but little information is available in the setting of preterm premature rupture of membranes (pPROM). We aimed to determine whether a short cervical length is independently associated with an increased risk of intra-amniotic infection or inflammation and impending preterm delivery in women with pPROM.. This was a retrospective cohort study involving 171 consecutive singleton pregnant women with pPROM (21+0-33+6 weeks' gestation), who underwent amniocentesis. Amniotic fluid (AF) was cultured, and assayed for interleukin (IL)-6 and IL-8. Cervical length was measured at the time of amniocentesis by transvaginal ultrasonography with an aseptic technique. Short cervical length was defined as a cervical length of ≤15 mm. Intra-amniotic infection was defined as a positive AF culture for microorganisms and intra-amniotic inflammation was defined as elevated AF concentrations of IL-6 or IL-8 (IL-6 ≥1.5 ng/mL and/or IL-8 ≥1.3 ng/mL).. Fifty (29.2%) women had a sonographic cervical length of ≤15mm. On univariate analysis, short cervical length was associated with an increased risk for intra-amniotic infection and/or inflammation; no other parameters studied showed a significant association. Multivariable analyses indicated that short cervical length was significantly associated with a higher risk of impending preterm delivery (within 2 days of measurement, within 7 days of measurement, and before 34 weeks), and remained significant after adjustment for potential confounders.. In women with pPROM, short cervical length is associated with an increased risk for intra-amniotic infection/inflammation and associated with impending preterm delivery, independent of the presence of intra-amniotic infection/inflammation.

Topics: Adult; Amniocentesis; Amniotic Fluid; Cervical Length Measurement; Cervix Uteri; Female; Fetal Membranes, Premature Rupture; Humans; Inflammation; Interleukin-6; Interleukin-8; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious

To evaluate whether levels of interleukin 6 (IL-6), interleukin 8 (IL-8), and vascular cell adhesion molecule-1 (VCAM-1) in women with premature rupture of membranes (PROM) differ from those in women without PROM.. An observational study of full-term primiparous pregnant women with PROM (PROM group) and those undergoing elective cesarean delivery (control group) was performed at a center in Yangzhou, China, between January 2003 and July 2006. IL-6, IL-8, and VCAM-1 levels were measured in maternal blood, cord blood, and amniotic fluid. A pathologic examination of fetal membranes was conducted.. The IL-6, IL-8, and VCAM-1 levels in maternal serum, amniotic fluid, and cord blood were significantly higher in the PROM group (n=58) than in the control group (n=38; P<0.05 for all comparisons). In the PROM group, the levels increased with duration of membrane rupture (P<0.05 for all). Women with chorioamnionitis had significantly higher levels than women without chorioamnionitis (P<0.05 for all), and women with PROM whose newborns had low Apgar score (≤7) had higher levels than those whose newborns had a higher Apgar score (P<0.05 for all).. Combined measurements of IL-6, IL-8, and VCAM-1 might help to improve early diagnosis of PROM and chorioamnionitis, and to evaluate the prognosis of newborns.

Topics: Adult; Amnion; Amniotic Fluid; Biomarkers; Cesarean Section; China; Chorioamnionitis; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Pregnancy; Prognosis; Vascular Cell Adhesion Molecule-1

To assess and compare several maternal seric markers for the prediction of histological chorioamnionitis (HCA) after preterm premature rupture of membranes (PPROM). Study design A prospective and multicentric observational study was undertaken, including six French tertiary referral centres. Pregnant women over 18 years, with PPROM between 22+0 and 36+6 WG were enrolled. A blood sample was obtained before delivery and analysed for C-Reactive Protein (CRP), InterCellular Adhesion Molecule-1 (ICAM-1), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Matrix-Metalloproteinase 8 and 9 (MMP-8, MMP-9), Triggering receptor on myeloid cells (TREM-1), and Human Neutrophile Peptides (HNP). HCA was determined by histological examination distinguishing maternal from fetal inflammatory response. Placental analyses and biological assays were performed in duplicate. Comparison of maternal seric markers levels in women with or vs. without HCA was performed, using a non-parametric Receiver Operating Characteristic.. 295 women were kept for analysis. The prevalence of HCA was 42.7% (126/295). The concentrations of MMP-8, MMP-9, HNP and CRP were higher in HCA vs. the non-HCA group (P<0.05) whereas the concentrations of ICAM- 1, IL-6, IL-8 were not different (P>0.05). The ROC curve with the largest AUC was for CRP (AUC; 0.70; 95% CI; 0.64-0.77) and it was significantly higher than those for MMP-8, MMP-9, or HNP (P<0.03).. CRP was the best maternal marker for predicting HCA in women with PPROM.

Topics: Adult; Biomarkers; C-Reactive Protein; Chorioamnionitis; Female; Fetal Membranes, Premature Rupture; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Membrane Glycoproteins; Placenta; Pregnancy; Prospective Studies; Receptors, Immunologic; Triggering Receptor Expressed on Myeloid Cells-1

Abstract Objective: To determine the cervical fluid interleukin (IL)-6 and IL-8 levels in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) and the association of these interleukins with microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA).. Sixty women with singleton pregnancies were included in this study. Cervical fluid was sampled at the time of admission using Dacron polyester swabs, which were placed into the endocervical canal for 20 s. IL-6 and IL-8 levels were determined by ELISA. The management of PPROM was active management (except for in pregnancies <28 weeks of gestation) and occurs not later than 72 h after the rupture of membranes.. The women with MIAC had higher IL-6 and IL-8 levels than did the women without MIAC (IL-6: p=0.01; IL-8: p=0.003). There was no difference in IL-6 levels between women with and without HCA (p=0.37). The women with HCA had higher IL-8 levels only in the crude analysis (p=0.01) but not after adjustment for gestational age (p=0.06). The women with both MIAC and HCA had higher levels of IL-6 and IL-8 than did the other women (IL-6: p=0.003; IL-8: p=0.001). IL-8 level of 2653 pg/mL was found to be the best cut-off point in the identification of PPROM pregnancies complicated by both MIAC and HCA with a likelihood ratio of 24.. The presence of MIAC is the most important factor impacting the local cervical inflammatory response, which is determined by IL-6 and IL-8 levels in the cervical fluid. IL-8 levels seem to be a promising non-invasive marker for the prediction of pregnancies complicated by the presence of both MIAC and HCA.

Topics: Adult; Amnion; Amniotic Fluid; Body Fluids; Cervix Uteri; Chorioamnionitis; Female; Fetal Membranes, Premature Rupture; Humans; Interleukin-6; Interleukin-8; Pregnancy; Pregnancy Complications, Infectious; Young Adult

To determine the vaginal fluid interleukin (IL)-6 and IL-8 concentrations in pregnancies complicated by preterm prelabor rupture of membranes and their correlation to microbial invasion of the amniotic cavity (MIAC) as well as histological chorioamnionitis (HCA).. Sixty-eight women with singleton pregnancies were included in this study. Vaginal fluid was collected at the time of admission. IL-6 and IL-8 concentrations in the vaginal fluid were determined using ELISA.. Women with MIAC had higher vaginal fluid IL-6 levels compared to those without MIAC (with MIAC: median 374 pg/mL versus without MIAC: median 174 pg/mL; p = 0.03). IL-8 levels were higher in women with MIAC only in the crude analysis but not after adjustment for gestational age. There was no difference in the IL-6 and IL-8 concentrations between those with and without HCA. Women with both MIAC and HCA had higher IL-6 vaginal fluid levels than those without both MIAC and HCA (with MIAC and HCA: median 466 pg/mL versus without MIAC and HCA: median 178 pg/mL; p = 0.02). IL-8 levels were higher in women with MIAC and HCA only in the crude analysis but not after adjustment for gestational age.. Vaginal fluid IL-6 but not IL-8 levels reflect the presence of MIAC and both MIAC and HCA.

Topics: Adult; Body Fluids; Chorioamnionitis; Cohort Studies; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Pregnancy; Pregnancy Complications, Infectious; Vagina; Young Adult

The maternal-fetal inflammatory response contributes to both preterm premature rupture of membranes (PPROM) and adverse neurological outcomes. Additionally, cytokines associated with fetal placental inflammation can be detrimental to brain development regardless of inciting infection. We investigated whether differential patterns of cytokine markers in maternal and fetal plasma samples reflect subtypes of placental inflammation and neurological outcomes at 6 months in infants born to mothers with PPROM.. Within a prospective cohort study of 25 women with PPROM, plasma cytokines (interleukin [IL]-1β, IL-6, IL-8, and tumor necrosis factor-α) were measured by enzyme-linked immunosorbent assay from maternal blood samples at rupture and delivery, and from fetal umbilical cord blood samples. Patterns of cytokine expression were correlated with specific placenta pathologies. Infants underwent cranial ultrasound after birth and standardized neurological examinations at 6 months' corrected gestational age. Predictors of inflammation and adverse neurological outcome were assessed by logistic regression, adjusting for gestational age at birth.. Inflammation of the fetal side of the placenta was associated with elevated maternal IL-6 and IL-8 at delivery and fetal IL-1β, IL-6, IL-8, and tumor necrosis factor-α. Worse neurological outcome at 6 months was associated with inflammation of the fetal side of the placenta and shorter duration from rupture of membrane to delivery, independent of gestational age at birth or cranial ultrasound results.. Our findings support the connection between fetal inflammation with adverse neurological outcome with PPROM, regardless of cranial ultrasound results. Further longitudinal studies are needed to adequately examine these patterns, and will aid in risk assessment and intervention strategies.

Topics: Adult; Chorioamnionitis; Cohort Studies; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Nervous System Diseases; Placenta; Pregnancy; Prospective Studies; Tumor Necrosis Factor-alpha; Young Adult

The aim of this study was to validate the results of an immunochromatographic bedside test to detect IL6 and IL8 in vaginal secretions after rupture of membranes (ROM) with results obtained by ELISA tests.. A prospective cohort of 60 women with ROM or preterm ROM (PROM) was recruited. An immunochromatographic bedside test was performed with vaginal secretions samplings at admission, every 48 hrs until labor and during labor. Remaining samples were frozen for ELISA analysis. The results of bedside tests were compared to those from ELISA analysis for 114 samples.. With all samples combined, the positive predictive values were 50% for IL6 and 86.8% for IL8 and the negative predictive values were 97.4% for IL6 and 53.3% for IL8. Kappa coefficients were 0.54 for IL6 and 0.41 for IL8.. Our findings show that a bedside test can detect the absence of IL6 in vaginal secretions. This result suggests that bedside test could be used for expectant management after premature PROM to inform the attending physician of the absence of inflammation in vaginal secretions.

Topics: Adult; Chorioamnionitis; Chromatography, Affinity; Enzyme-Linked Immunosorbent Assay; Female; Fetal Membranes, Premature Rupture; Humans; Inflammation; Interleukin-6; Interleukin-8; Predictive Value of Tests; Pregnancy; Sensitivity and Specificity; Vagina; Young Adult

To determine whether interleukin (IL)-1β, IL-6, and IL-8 in cervicovaginal fluid, alone or in combination with clinical risk factors, could predict intra-amniotic infection in women with preterm premature rupture of membranes (PPROM).. A prospective cohort study.. University teaching hospital.. Women with singleton pregnancies presenting PPROM between 20 and 35 weeks of gestation (n = 76).. Cervicovaginal fluid samples were collected for IL-1β, IL-6, and IL-8 measurements immediately before amniocentesis. Amniotic fluid obtained by amniocentesis was cultured and the white blood cell count was determined. Clinical risk factors analyzed included demographics and gestational age. Cervicovaginal concentrations of cytokines were measured using a multiplex bead array assay.. A positive amniotic fluid culture.. The prevalence of a positive amniotic fluid culture was 46.1% (35/76). Stepwise multivariate regression analysis yielded a model using cervicovaginal IL-6 and gestational age at sampling with the area under the curve (AUC) of 0.807 for predicting intra-amniotic infection. The AUC for this model was significantly higher than either parameter retained in this model but no differences were observed between the AUC of this model based on non-invasive variables, and amniotic fluid white blood cell count using invasive amniocentesis for the prediction of intra-amniotic infection.. Among measured cytokines, the combination of cervicovaginal IL-6 and gestational age appears to be best in predicting intra-amniotic infection and allows for a considerably better accuracy than the use of either factor alone. Overall, this combination performed as well as amniotic fluid WBC count for predicting intra-amniotic infection.

Topics: Adult; Amniotic Fluid; Cervix Uteri; Chorioamnionitis; Cohort Studies; Cytokines; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Leukocyte Count; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Infectious; Prospective Studies; Risk Factors; Vagina

The aim of this study was to determine whether amniotic fluid levels of annexin A2, a phospholipid-binding protein that is abundant in amnion and regulates fibrin homeostasis, are associated with histological chorioamnionitis, preterm premature rupture of the membranes, and subsequent preterm delivery.. Amniotic fluid was obtained from 55 pregnant women with preterm labor and/or preterm premature rupture of the membranes before 32weeks of gestation, and amniotic fluid levels of annexin A2 were measured with a sandwich enzyme-linked immunosorbent assay.. Amniotic fluid levels of annexin A2 in patients with histological chorioamnionitis was higher than that in the remainder (P=0.053), whereas amniotic fluid levels of annexin A2 in patients with preterm premature rupture of the membranes was significantly higher than that in the remainder (P=0.002). Amniotic levels of annexin A2 was a fair test (area under receiver-operator characteristic curve=0.679), and amniotic fluid levels of annexin A2>878.2ng/mL had a sensitivity of 68.8%, a specificity of 65.2%, a positive predictive value of 73.3%, and a negative predictive value of 60.0% for predicting delivery within 2weeks after amniotic fluid sampling. Furthermore, the combined use of amniotic fluid cut-off levels of 878.2ng/mL for annexin A2 and 13.3ng/mL for interleukin-8 improved the specificity (91.3%) and the positive predictive value (89.5%).. We identified amniotic fluid levels of annexin A2, especially in combination with amniotic fluid levels of interleukin-8, as a novel predictive marker for preterm delivery.

Topics: Adult; Amniotic Fluid; Annexin A2; Chorioamnionitis; Female; Fetal Membranes, Premature Rupture; Humans; Interleukin-8; Predictive Value of Tests; Pregnancy; Premature Birth

Activins and inhibins are important modulators of inflammatory processes. We explored activation of amniotic fluid (AF) activin-A and inhibin-A system in women with intra-amniotic infection and preterm premature rupture of the membranes (PPROM).. We analyzed 78 AF samples: '2nd trimester-control' (n=12), '3rd trimester-control' (n=14), preterm labor with intact membranes [positive-AF-cultures (n=13), negative-AF-cultures (n=13)], and PPROM [positive-AF-cultures (n=13), negative-AF-cultures (n=13)]. Activin-A levels were evaluated ex-vivo following incubation of amniochorion and placental villous explants with Gram-negative lipopolysaccharide (LPS) or Gram-positive (Pam3Cys) bacterial mimics. Ability of recombinant activin-A and inhibin-A to modulate inflammatory reactions in fetal membranes was explored through explants' IL-8 release.. Activin-A and inhibin-A were present in human AF and were gestational age-regulated. Activin-A was significantly upregulated by infection. Lower inhibin-A levels were seen in PPROM. LPS elicited release of activin-A from amniochorion, but not from villous explants. Recombinant activin-A stimulated IL-8 release from amniochorion, an effect that was not reversed by inhibin-A.. Human AF activin-A and inhibin-A are involved in biological processes linked to intra-amniotic infection/inflammation-induced preterm birth.

Topics: Activins; Amniotic Fluid; Female; Fetal Membranes, Premature Rupture; Humans; Inhibins; Interleukin-6; Interleukin-8; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Premature Birth

Intrauterine infection and inflammation are recognized as major contributors to the onset of preterm labor. We describe two cases of severe preterm labor with bulging membrane that were treated by intravenous injection of Sivelestat, a neutrophil elastase inhibitor. Ritodrine hydrochloride and magnesium sulfate were intravenously administered for tocolysis, and ampicillin was provided as an antibiotic. Urinary trypsin inhibitor (UTI) was administered transvaginally. Sivelestat was infused intravenously at 4.8 mg kg(-1) day(-1) through the maternal vein. No side effects were observed. Levels of interleukin (IL)-6 and IL-8 in amniotic fluid decreased, and gestations were prolonged without complications for >1 week. Two healthy infants were delivered. Our experience suggests that multidrug therapy with Sivelestat offers a new therapeutic strategy for preterm labor, but further investigations of the indications, administration period and dosage are required.

Topics: Adult; Amniotic Fluid; Female; Fetal Membranes, Premature Rupture; Glycine; Humans; Injections, Intravenous; Interleukin-6; Interleukin-8; Magnesium Sulfate; Obstetric Labor, Premature; Pregnancy; Ritodrine; Serine Proteinase Inhibitors; Sulfonamides; Tocolytic Agents; Young Adult

To determine whether umbilical cord blood concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), and matrix metalloproteinase-8 (MMP-8) are of value in the diagnosis of histological chorioamnionitis (HCA) and funisitis in patients with preterm premature rupture of membranes (PPROM).. Department of Obstetrics and Gynaecology, Charles University in Prague, Faculty of Medicine Hradec Kralove, University Hospital Hradec Kralove, Czech Republic.. We compared umbilical cord blood IL-6, IL-8, and MMP-8 concentrations in 83 women with PPROM between 24th and 36th gestational weeks with the presence and the absence of HCA/funisitis using nonparametric tests (Mann-Whitney U test), given the non-normal distribution of analyte. Comparisons of proportions were performed the D'Agostino and Pearson omnibus normality test and the Shapiro-Wilk test.. Patients with HCA had a significantly higher median umbilical cord blood IL-6 concentration than patients without histological signs of inflammation (12.0 pg/mL [2.1-138.3] versus 2.7 pg/mL [0.1-12.4]; p=0.004) but did not have significantly higher median umbilical cord IL-8 (29.9 pg/mL [14.0-186.3]; versus 18.9 pg/mL [7.9-89.4]; p=0.13) and MMP-8 (2.9 pg/mL [0.5-25.2] versus 0.5 ng/mL [0.5-7.9]; p=0.18). Patients with HCA and funisitis had a significantly higher median umbilical cord blood IL-6 (222 pg/mL [95.3-411.7] versus 6.1 pg/mL [1.3-18.5]; p<0.0001) and IL-8 (20.9 pg/mL [8.4-37.7] versus 190.7 pg/mL [83.8-554.2]; p=0.0004) concentration than patients with HCA alone. Differences were not found in MMP-8 concentrations (3.7 ng/mL [0.5-21.4] versus 2.4 ng/mL [0.5-88.1]; p=0.7).. HCA was associated with a significant increase in umbilical cord blood IL-6 concentration. In patients with HCA and funisitis, umbilical cord blood IL-6 and IL-8 were significantly higher than those without histological signs of inflammation.

Topics: Adult; Biomarkers; Chorioamnionitis; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Fetus; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 8; Pregnancy

To quantify the expression of interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor alpha (TNF-alpha) in chorioamniotic membranes of PPROM pregnant women with chorioamnionits.. The study included 25 PPROM women in labor, 15 PPROM without labor, and 25 pregnant women in preterm labor (PTL). Chorioamniotic membranes were collected for histopathological analyses and cytokine mRNA expression quantification by real time PCR. Comparisons were performed using the Mann-Whitney, Kruskal-Wallis, Fisher's exact test or z test with significance set at p<0.05. The software employed was the SigmaStat version 3.1.. During the study PPROM incidence was 4.6% and chorioamnionits was present in 75% of the samples. IL-1beta, IL-6, and IL-8 mRNA expression did not statistically differ among study groups. TNF-alpha mRNA expression was statistically higher in PTL. No difference in the mRNA concentration of the cytokines studied in the presence of chorioamnionitis was observed.. Chorioamniotic membranes are sources of IL-1beta, IL-6, IL-8, and TNF-alpha and their mRNA concentrations in PPROM are not related to the presence of chorioamnionitis.

Topics: Adult; Amnion; Case-Control Studies; Chorioamnionitis; Chorion; Extraembryonic Membranes; Female; Fetal Membranes, Premature Rupture; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Labor Stage, First; Obstetric Labor, Premature; Pregnancy; RNA, Messenger; Tumor Necrosis Factor-alpha

In the present study, we investigated the participation of inflammatory cytokine-induced mediated matrix metalloproteinase (MMP) expressions and inhibition of interleukin (IL)-6-induced MMP secretion in amniotic epithelial cells by tocilizumab.. To investigate the role of MMP expressions, immunohistochemical staining was performed using membranes obtained from 10 patients with preterm premature rupture of membranes (PPROM) and from 10 patients who underwent a nonlabor cesarean section. We also investigated the regulation of MMP expression by inflammatory cytokines in human amnion cells.. Immunohistochemical staining showed a significantly higher expression of MMP-2 and -9 in PPROM. Treatment of cultured WISH and primary amniotic epithelial cells with 10(-8) or 10(-7)M IL-6 or tumor necrosis factor (TNF)-alpha clearly increased the secretion of MMP-2 and -9. Treatment with 10(-8)M TNF-alpha or IL-6 significantly increased the invasion of WISH or primary amniotic epithelial cells, respectively, compared with the control. At a low concentration of 1 microg/ml, tocilizumab (anti-human IL-6 receptor monoclonal antibody) inhibited the IL-6-induced MMP secretion.. This paper is the 1st report of tocilizumab inhibiting IL-6-induced MMP-2 and MMP-9 secretions from human amnion cells in PPROM.

Topics: Amnion; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Blotting, Western; Cell Line; Epithelial Cells; Female; Fetal Membranes, Premature Rupture; Humans; Immunohistochemistry; Interleukin-1beta; Interleukin-6; Interleukin-8; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Peptide Fragments; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha

Some studies showed increased levels ofproinflammatory cytokines like IL-6, IL-8 and TNF-alpha in the blood samples of pregnant women with PROM (Premature rupture of membranes) and their neonates. The aim of this study was to find a relationship between increased level of IL-8 and PROM, a cost benefit method for early diagnosis and reduction of hospitalization period of neonatal sepsis. This case control study was conducted in Obstetrics and Gynecology Department of Al-Zahra Hospital at Tabriz University of Medical Sciences, Iran from 10th April 2001 to 20th June 2003. We studied 50 LBW (Low birth weight) neonates born from mothers with PROM as the case group and fifty LBW neonates born from mothers without PROM as our control group Neonates born from pregnant women with PROM underwent sepsis workup and blood samples from their umbilical cord were sent for blood culture and IL-8 level measurement. Mean levels of IL-8 in study and control groups were 128.12 and 39.2 pg mL(-1), respectively. We had no positive blood culture and no bacteria could be isolated. Significantly elevated values (p<0.0003) were showed in cases with PROM compared to cases without PROM (medians 67.5 pg mL(-1) vs. 29.5 pg mL(-1), respectively). This study showed a strong relationship between IL-8 elevation and PROM. Increased levels of IL-8 can be used as indicator for early diagnosis of neonatal sepsis.

Topics: Case-Control Studies; Extraembryonic Membranes; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; Interleukin-8; Male; Pregnancy; Sepsis

To determine whether amniotic fluid levels of interleukin-8 (IL-8) are of value in the antenatal diagnosis of acute histological chorioamnionitis (HCA) in preterm premature rupture of membranes (PPROM).. Department of Obstetrics and Gynaecology, Charles University, Medical School and University Hradec Kralove, Czech Republic.. We compared amniotic fluid IL-8 levels in twenty-nine pregnant women with preterm premature rupture of membranes between 24th and 36th gestational weeks with presence and absence acute histological chorioamnionitis or/and microbial invasion in the amniotic cavity using nonparametric tests (Mann-Whitney test), given the non-normal distribution of analyte. Comparisons of proportions were performed with Shapiro-Wilk normality test.. Patients with HCA had a significantly higher median amniotic fluid IL-8 concentration than patients without the histological signs of chorioamnionitis (1867 pg/mL, 826-5577 versus 1045 pg/mL, 60-4133, p=0.013). Patients with MIAC had a significantly higher median amniotic fluid level than patients without invasion (1888 pg/mL, 519-5577 versus 1225 pg/mL, 60-2766, p= 0.017). Women with HCA and MIAC had a significantly higher median amniotic fluid IL-8 level than women without histological signs of chorioamnionitis and microbial invasion (3117 pg/mL, 826-5577 versus 1468 pg/mL, 394-2766, p=0.034).. HCA or/and MIAC are associated with a significant increase of amniotic fluid interleukin-8 levels. Amniotic fluid IL-8 seems to be a marker of intraamniotic inflammation.

Topics: Adult; Amniotic Fluid; Biomarkers; Chorioamnionitis; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-8; Predictive Value of Tests; Pregnancy; Prospective Studies; Ureaplasma; Ureaplasma Infections

The purpose of this study was to determine cord blood cytokine levels and their relationship with morbidity and mortality in neonates with prolonged, premature rupture of membranes (PPROM). Forty two premature neonates of 29-35 weeks gestational age with PPROM exceeding 24 hours were considered as the PPROM group and simultaneously, 41 premature neonates without PPROM were considered as the control group. All the neonates were admitted to the Neonatology Unit for further evaluation of subsequent complications such as early neonatal sepsis, pneumonia, intraventicular haemorrhage (IVH), respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC) and chronic lung disease (CLD). Cord blood and mothers' blood samples were obtained during delivery in both groups and tested for IL-6, IL-8 and TNF-alpha levels. Twenty one percent of patients with PPROM had histological chorioamnionitis. The risk for developing early neonatal sepsis increased significantly in neonates whose mothers had histological chorioamnionitis (p < 0.05). There was a statistically significant relationship between PPROM and risk of developing NEC (p < 0.05); no significant increase was seen as regards early neonatal sepsis, IVH, RDS, pneumonia, or BPD. The mean IL-8 levels in cord blood and mothers' serum were significantly higher in the PPROM group (p < 0.001, p< 0.005). In addition, IL-6 levels found in mothers' serum were significantly higher than those found in the control group (p < 0.01). However, levels in cord blood were similar (p > 0.05). TNF-alpha levels were similar in both groups (p > 0.05). Neonates who developed NEC had higher IL-8 levels in their cord blood when compared to those without NEC (p < 0.05). In conclusion, the presence of PPROM increases the risk of chorioamnionitis. In addition, PPROM increases the risk of NEC, and patients who developed NEC had significantly higher cord blood IL-8 values. We may conclude that patients with PPROM and higher IL-8 levels in cord blood might be considered as at possible risk of NEC.

Topics: Adult; Chorioamnionitis; Cytokines; Enterocolitis, Necrotizing; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Infant, Premature; Interleukin-6; Interleukin-8; Neonatology; Pregnancy; Risk; Sepsis

Preterm premature rupture of the membranes (PROM) has been attributed to ascending infection and a choriodecidual inflammatory response (ie, on the maternal side). However, on the fetal side those most at risk of morbidity have a systemic proinflammatory cytokine response. We have recently defined a similar proinflammatory response in pregnancies complicated by vascular disease on the fetal side of the placenta. A factor(s) present in fetal plasma from these pregnancies can stimulate human umbilical vein endothelial cells (HUVECs) to express mRNA for the proinflammatory cytokines, interleukin (IL)-6 and IL-8. The hypothesis of this study was that a similar factor(s) was present in preterm PROM.. A standard culture of HUVECs was incubated with fetal plasma, obtained immediately following delivery, from normal pregnancies delivering vaginally at term (n=16) and pregnancies delivering following preterm PROM (n=19). Expression of mRNA for IL-6 and IL-8 was assessed by reverse transcription polymerase chain reaction (RT-PCR) and standardized to GAPDH mRNA expression.. Endothelial cell expression of IL-6 mRNA (median [25-75th centile] 0.295 [0.252-0.507] vs term vaginal delivery 0.208 [0.151-0.307]; P=.009) was enhanced in response to the fetal plasma from PROM cases compared to pregnancies delivering vaginally at term. In contrast, mRNA expression of IL-8 (median [25-75th centile] preterm PROM 0.41 [0.21-0.78] vs term vaginal delivery 0.49 [0.16-0.68]; P=.46) was not different in the two groups.. We have demonstrated that in fetuses delivered following preterm PROM there is a factor(s) capable of stimulating a local endothelial cell proinflammatory cytokine (IL-6) response. This factor(s) that we have demonstrated may be responsible for the increased cytokine production seen in fetuses with the fetal inflammatory response syndrome.

Topics: Endothelium, Vascular; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Recent evidence has linked preterm premature rupture of the fetal membranes (PPROM) to placental abruption. Because neutrophils are a rich source of proteases that can degrade extracellular matrix in abruption-associated PPROM, we examined whether decidual neutrophil infiltration complicates abruption-associated PPROM. Accordingly, immunostaining for the neutrophil marker CD15 was performed in placentas obtained after overt abruption (decidual hemorrhage) with or without PPROM and in control placentas. Abruptions were associated with a marked decidual neutrophil infiltration that peaked after PPROM, whereas decidua from gestational age-matched controls were virtually devoid of neutrophils. Neutrophil infiltrates co-localized with fibrin deposition. Because abruptions elicit intense decidua-enhanced thrombin production, we examined the regulation of abruption-induced neutrophil infiltration. Expression of the primary neutrophil chemoattractant interleukin-8 (IL-8) was evaluated in leukocyte-free term decidual cells incubated with estradiol (E2; control) or with E2+medroxyprogesterone acetate (to mimic pregnancy)+/-thrombin. After 24 hours, enzyme-linked immunosorbent assay measurements indicated that thrombin (0.1 to 2.5 U/ml) elicited a dose-dependent elevation in secreted IL-8 (P<0.05) with 2.5 U/ml of thrombin increasing IL-8 levels by >14-fold in E2 and E2+medroxyprogesterone incubations. Results were validated by Western blot and quantitative reverse transcriptase-polymerase chain reaction. In summary, thrombin-enhanced IL-8 expression in term decidual cells may explain how abruption-associated PPROM promotes decidual neutrophil infiltration.

Topics: Abruptio Placentae; Adult; Blotting, Western; Cells, Cultured; Decidua; Enzyme-Linked Immunosorbent Assay; Estradiol; Female; Fetal Membranes, Premature Rupture; Fibrin; Humans; Immunohistochemistry; Interleukin-8; Lewis X Antigen; Medroxyprogesterone Acetate; Neutrophil Infiltration; Neutrophils; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thrombin

Previous studies have shown an association between intra-amniotic microbial invasion and/or inflammation and spontaneous preterm birth. The aim of this study was to investigate the occurrence of intra-amniotic microorganisms and cytokines [interleukin (IL)-6 and IL-8] in a Swedish population, with low incidence of preterm birth, of women with preterm prelabor rupture of membranes and their correlation to preterm birth.. Amniotic fluid was retrieved transabdominally from 58 patients with preterm prelabor rupture of membranes before 34 weeks of gestation. Polymerase chain reaction (PCR) analyses for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. IL-6 and IL-8 were analyzed with enzyme-linked immunosorbent assay (ELISA).. Microorganisms in amniotic fluid were detected in 13 patients (25%). Patients with bacteria detected in the amniotic fluid had significantly higher levels of IL-6 and IL-8. An amniotic fluid concentration of IL-6 >/= 0.80 ng/ml [relative risk 1.93, 95% confidence interval (CI) 1.13-3.29, sensitivity 63%, specificity 75%] was associated with an increased risk of delivery within 7 days. There was also an association between IL-8 and preterm birth (< 34 weeks).. Intra-amniotic microbial invasion and inflammation in this population of Swedish women with preterm prelabor rupture of membranes were similar to data reported from populations with a higher incidence of preterm delivery. Amniotic IL-6 correlated to the presence of microorganisms and delivery within 7 days and IL-8 to delivery before 34 weeks.

Topics: Adult; Amniocentesis; Amniotic Fluid; Bacteria, Aerobic; Bacteria, Anaerobic; Enzyme-Linked Immunosorbent Assay; Female; Fetal Membranes, Premature Rupture; Humans; Interleukin-6; Interleukin-8; Logistic Models; Mycoplasma hominis; Obstetric Labor, Premature; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Prospective Studies; Risk Factors; Sweden; Ureaplasma urealyticum

The placenta and fetal membranes are the site of expression of macrophage inhibitory cytokine (MIC-1), a member of the transforming growth factor (TGF)-beta superfamily. We hypothesized that MIC-1 may act as an immune regulator in pregnancy complications associated with intrauterine inflammation. Decidual cells, chorionic trophoblasts and amnion epithelial cells were identified by immunohistochemistry as the predominant MIC-1-containing cell type in term membranes. Amnion and choriodecidual explants all produced MIC-1 in culture, the latter having the greatest production rate (206 +/- 74.5 pg/mg tissue/24 h, n=6; mean +/- SEM). Production was not responsive to stimulation by pro-inflammatory cytokines. MIC-1 was detectable in 217 transabdominal amniotic fluid (AF) samples taken from 15 to 41 weeks gestation, concentrations ranging from 0.9-51.1 ng/ml. AF MIC-1 concentrations in pregnancies with premature rupture of membranes (PROM) or preterm labour, either with or without microbial invasion of the amniotic cavity, were not significantly different from those delivered at term either with or without labour. Treatment with MIC-1 (0.25-25 ng/ml) did not alter production of interleukin-6 or -8 by amnion or choriodecidual cells in vitro. We conclude that AF MIC-1 is derived from the fetal membranes and decidua, but that MIC-1 is unlikely to be involved in the pathophysiology of preterm birth or PROM.

Topics: Amniotic Fluid; Cytokines; Extraembryonic Membranes; Female; Fetal Membranes, Premature Rupture; Growth Differentiation Factor 15; Humans; Immunohistochemistry; Interleukin-6; Interleukin-8; Obstetric Labor, Premature; Pregnancy

Cytokines may be implicated in the pathophysiologic mechanisms of preterm and term labor. Many studies indicate cytokines as predictors of preterm delivery and explain partially mechanism of preterm uterine contractions. Complicated relations between mediators in systemic fluids of a fetomaternal unit require further explorations. The right diagnosis and management require better understanding of these relationships.. The comparison of IL-1 alpha, IL-1 beta, IL-6 and IL-8 levels in maternal serum and amniotic fluid in term and preterm labor complicated by PROM.. In 44 patients in premature labor with PROM (group I) and 33 patients in labor at term with PROM (group II) cytokines levels were estimated one time in amniotic fluid: just after PROM, and two times in maternal serum: just after PROM and during labor.. Amniotic fluid cytokines levels were significantly higher in group I than in group II. Maternal serum cytokines concentrations of IL-1 alpha and IL-1 beta in group I were significantly higher than in group II. IL-6 level was significantly higher in group II than in group I. In both groups maternal serum IL-6 levels during labor significantly increased in comparison to IL-6 levels just after PROM. No correlations between amniotic fluid and maternal serum cytokine levels at PROM were observed.. Higher amniotic fluid cytokines levels in patients with preterm labor complicated by PROM than in labor at term with PROM indicate possible differences between PROM mechanisms in preterm and term labor. The increase of IL-6 level during labor can be related with the possible role of this cytokine in the immunological mechanism of the labor beginning. No relationships between amniotic fluid and maternal serum levels of investigated cytokines in PROM suggest the presence of the barrier stopped cytokines transfer by the placenta and the complete separation of these two compartments.

Topics: Adult; Amniotic Fluid; Enzyme-Linked Immunosorbent Assay; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Interleukin-1; Interleukin-6; Interleukin-8; Interleukins; Obstetric Labor, Premature; Pregnancy; Risk Factors; Time Factors

Cytokine plasma levels are suggested to be sensitive indicators of neonatal sepsis, but conventional assays are time consuming. This study aimed at evaluating the significance of cord blood levels of interleukin (IL)-6 and IL-8 determined by a fully automated random access assay within 90 min of admission to predict systemic bacterial infection.. Cord blood levels of IL-6 and IL-8 were determined in 71 mature and 100 premature infants by a chemiluminescence assay (Immulite). Patients were divided into four groups according to a clinical and laboratory scoring system. Group A: documented early-onset infection; group B: infection possible; group C: infection unlikely, and group D: healthy newborns.. Median IL-6 levels in the subgroup of premature newborns were as follows: group A, 1,920 pg/ml (5-95% confidence interval 308-4,660 pg/ml); group B, 50 (15-102) pg/ml; group C, 21 (12-71) pg/ml, and group D, 8 (6-11) pg/ml. For IL-8, median levels for groups A-D were 289 (226-514) pg/ml, 87 (40-107) pg/ml, 44 (33-98) pg/ml and 21 (16-25) pg/ml, respectively. The difference between group A and the other groups was highly significant (IL-6 p < 0.0001, IL-8 p < 0.001). At a cut-off of 80 pg/ml, the sensitivity of IL-6 for the diagnosis of sepsis was 96% (specificity 95%). For IL-8 (cut-off 90 pg/ml), the sensitivity was 87% (specificity 94%).. In premature infants, the diagnosis of an early-onset infection can be established or ruled out with a high level of confidence by measuring IL-6 or IL-8 levels from cord blood using a random access chemiluminescence assay.

Topics: Apgar Score; C-Reactive Protein; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-6; Interleukin-8; Male; Pregnancy; Sensitivity and Specificity; Sepsis

To study the changes in interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) levels in patients with premature rupture of the membranes (PROM).. A total of 46 normal term pregnant women served as controls and 46 women with PROM were enrolled for study. Maternal serum and amniotic fluid IL-6, IL-8 and TNF-alpha levels were determined by enzyme-linked immunosorbent assay and a sensitive radioimmunoassay, respectively.. The maternal serum IL-6 and IL-8 levels and amniotic fluid IL-6, IL-8 and TNF-alpha levels were higher than those of controls, and the differences were significant between the two groups (p < 0.05). Although the levels of TNF-alpha in maternal serum were higher than that of controls, the difference was not significant. There were significant relationships between the levels of IL-6, IL-8 and TNF-alpha and the duration of PROM. The longer the duration of PROM, the higher the levels of maternal serum and amniotic fluid IL-6, IL-8 and TNF-alpha were. There were 12 cases of clinical chorioamnionitis, and the levels of IL-6, IL-8 and TNF-alpha in the maternal and amniotic fluid were higher than that of those without chorioamnionitis (p < 0.05).. Determining cytokines (IL-6, IL-8 and TNF-alpha) is a valuable clinical method for identifying chorioamnionitis in patients with PROM.

Topics: Adult; Amniotic Fluid; Cytokines; Female; Fetal Membranes, Premature Rupture; Humans; Interleukin-6; Interleukin-8; Pregnancy; Tumor Necrosis Factor-alpha

The aim of this prospective study was to examine if serum concentrations of cytokines are of value in the identification of patients at risk for preterm delivery.. Interleukin- 1beta,2,4,6,8 and tumor necrosis factor alpha were determined between 25 and 37 weeks of gestation in the serum of 72 consecutive patients with preterm labor, 38 patients with preterm rupture of the membranes, and 24 healthy pregnant women as a control group. Material was collected within 18 hours after hospitalization and was immediately centrifuged and shock frozen.. Significantly increased serum levels were found for interleukin-6 and -8 in patients with preterm labor or preterm rupture of the membranes when compared to the control group (p<0.001 and p<0.005, respectively). In patients with preterm rupture of the membranes and interleukin-6 levels above the median of 4.0 pg/ml the delivery occurred significantly earlier than in patients with lower levels (1 versus 5.5 days; p=0.005). Patients of both pathology groups with detectable (>18 pg/ml). Interleukin-8 levels had a shorter pregnancy duration when compared to other patients (p=0.05 for preterm labor and p=0.04 for preterm rupture of the membranes). Interleukin-1beta,2,4, and tumor necrosis factor alpha were not correlated with clinical outcome.. Increased serum interleukin-6 and -8 levels are associated with a shorter interval between onset of preterm rupture of the membranes and delivery and should therefore be further evaluated for their use in clinical practice.

Topics: Adult; Female; Fetal Membranes, Premature Rupture; Humans; Interleukin-6; Interleukin-8; Obstetric Labor, Premature; Predictive Value of Tests; Pregnancy; Prospective Studies; Risk Assessment; Sensitivity and Specificity

To determine if an intrauterine sub-clinical inflammatory process is a risk factor for the development of bronchopulmonary dysplasia.. A cohort study was conducted in patients who met the following criteria: (1) Singleton gestation; (2) preterm labor or preterm premature rupture of the membranes; (3) amniocentesis for microbiologic studies of the amniotic fluid and (4) delivery between 24 and 28 weeks of gestation. Bronchopulmonary dysplasia was defined as the need for supplemental oxygen for 28 days or longer after birth, associated with compatible chest radiographic findings. Amniotic fluid interleukin-8, was measured using a specific immunoassay. Logistic regression analysis and bootstrap procedure were used for statistical purposes.. Forty-seven patients met the inclusion criteria for this study. Among these patients, the prevalence of bronchopulmonary dysplasia was 23.4% (11/47). Amniotic fluid culture was positive in 21 out of 47 (44.7%) patients. Median (range) amniotic fluid interleukin-8 concentration was higher in patients whose neonates subsequently developed bronchopulmonary dysplasia than in those who did not (17 [9.8-583.7] ng ml(-1) versus 9.6 [0.91-744] ng ml(-1), P=0.057). An amniotic fluid IL-8 level greater than 11.5 ng ml(-1) was far more common in mothers whose fetuses went on to develop bronchopulmonary dysplasia than in those who did not (10/11 [90.9%] versus 17/36 [47%]; P=0.01). This relationship remained significant even after correcting for the effect of gestational age and birthweight (Odds ratio: 11.9; P<0.05).. Sub-clinical intrauterine inflammation is a risk factor for the subsequent development of bronchopulmonary dysplasia. We propose that in utero aspiration of fluid with high concentration of pro-inflammatory mediators may contribute to the lung injury responsible for the development of bronchopulmonary dysplasia.

Topics: Amniotic Fluid; Birth Weight; Bronchopulmonary Dysplasia; Cohort Studies; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-8; Logistic Models; Mycoplasma hominis; Obstetric Labor, Premature; Pregnancy; Risk Factors; Ureaplasma urealyticum

To study the relationship of maternal blood and amniotic fluid cytokine levels in patients with preterm premature rupture of membrane and chorioamnionitis.. IL8 and TNF alpha levels of maternal blood and amniotic fluid were determined by 125I radioimmunoassay (RIA) and an enzyme-labeled immunosorbent assay (ELISA). Chorioamnionitis was diagnosed by fetal membrane histology.. The maternal serum IL8 levels and amniotic fluid IL8, TNF alpha levels were higher than those of controls (P < 0.05). There was significant relationship between maternal serum and amniotic fluid IL8, TNF alpha with the time of the premature rupture of membanes. The longer the time the higher the maternal serum IL8 and amniotic fluid IL8, TNF alpha; There were 13 patients with chorioamnionitis, and their maternal serum and amniotic fluid IL8, TNF alpha were higher than those of patients with non-chorioamnionitis (P < 0.01-0.05).. IL8, TNF alpha levels of maternal serum and amniotic fluid are valuable clinical indexes in identification of chorioamnionitis in patients with preterm premature rupture of membranes.

Topics: Adult; Amniotic Fluid; Chorioamnionitis; Female; Fetal Membranes, Premature Rupture; Humans; Interleukin-8; Pregnancy; Tumor Necrosis Factor-alpha

Interleukin-8 (IL-8), a 72 amino acid peptide secreted by cells of the immune system and of the amnion, chorion and decidua, was measured in women in late pregnancy. IL-8 was detected in the urine of 91 of 104 women with premature rupture of the fetal membranes, with values exceeding 1000 ng/L in cases of severe intra-amniotic infection. Women with urinary tract infections were excluded. The routine measurement of IL-8 in urine, together with C-reactive protein in serum, thus provides a low risk and technically simple approach to the assessment of intra-amniotic infection.

Topics: Amnion; Enzyme-Linked Immunosorbent Assay; Female; Fetal Membranes, Premature Rupture; Humans; Interleukin-8; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Prenatal Diagnosis; Sensitivity and Specificity

Preterm labor and premature rupture of the membranes are major complications of pregnancy. We have reported the possible role of amniochorionic membrane in the production of inflammatory cytokines and the early onset of labor. This study was conducted to detect the expression of IL-8 mRNA and peptide production in cultured fetal membranes.. Amniochorionic membranes were collected from women undergoing elective cesarean section at term. Membranes were cultured in an organ explant system and the expression of IL-8 was studied over a 10-day period by RT-PCR and in situ hybridization. IL-8 peptide localization was accomplished using immunocytochemistry.. Constitutive expression of IL-8 mRNA in cultured fetal membranes was demonstrated in both amniotic and chorionic leave cells. mRNA and peptide for IL-8 was homogeneously distributed throughout the amniotic and chorionic cells.. Human amniochorionic membrane is a source of IL-8 mRNA and peptide.

Topics: Amnion; Chorion; Female; Fetal Membranes, Premature Rupture; Humans; In Situ Hybridization; Interleukin-8; Organ Culture Techniques; Peptide Biosynthesis; Polymerase Chain Reaction; Pregnancy; RNA, Messenger

Interleukin-8 (IL-8) exerts chemotactic activity on neutrophils at inflammatory sites to eliminate invading bacteria. To investigate whether the preterm fetus with chorioamnionitis produces IL-8, the titers of IL-8 were examined in sera of babies with (n = 38) and without chorioamnionitis (n = 34) using an EIA kit specific for IL-8. The infected babies had a significantly higher IL-8 titer than those not infected at 22-36 gestational weeks. The IL-8 titer was increased even in the mild histologic stage of chorioamnionitis and became much higher in the more severe stage. The IL-8 elevation, however, was remarkably suppressed by infusion of a steroid into the mother to promote fetal lung maturation. This retrospective study demonstrated that titration of IL-8 in cord serum is a more useful marker for the early detection of chorioamnionitis, because of its higher sensitivity and specificity, than conventional markers such as C-reactive protein.

Topics: Anti-Bacterial Agents; Betamethasone; Chorioamnionitis; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Fetal Organ Maturity; Humans; Infant, Newborn; Interleukin-8; Lung; Obstetric Labor, Premature; Pregnancy; Retrospective Studies; Sensitivity and Specificity