Cytokine and prostaglandin production by amnion cells in response to the addition of different bacteria (original) (raw)
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Diversity in cytokine response to bacteria associated with preterm birth by fetal membranes
American Journal of Obstetrics and Gynecology, 2009
This study compared cytokine and prostaglandin (PG) responses by fetal membranes stimulated with 4 different bacterial species associated with preterm birth (PTB). STUDY DESIGN: Fetal membranes (n ϭ 13 from normal term cesarean sections [not in labor]) in an organ explant system were stimulated with heat-killed Ureaplasma parvum, Gardanerella vaginalis, Escherichia coli, group B Streptococcus (GBS), or lipopolysaccharide (LPS). Cytokines (interleukin [IL]-1, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-␣, and interferon-␥) and PG (PGF 2␣ and PGE 2) concentrations were quantitated and compared. RESULTS: LPS and E coli increased all cytokine and PG productions compared with controls. Cytokine profiles were similar after G vaginalis and GBS stimulation. G vaginalis increased PGE 2 , whereas GBS increased PGF 2␣. U parvum demonstrated the mildest response with only IL-10 and TNF-␣ concentrations being higher with no detectible effect on PGs. CONCLUSION: Fetal membrane cytokine signatures of 4 different bacteria associated with PTB are distinct, suggesting that infection as a potential cause of PTB is not homogeneous in its presentation.
American Journal of Reproductive Immunology, 2011
Problem We compared the frequency of intra-amniotic infection in preterm labor (PL) with women not in labor, and correlated infection with amniotic fluid (AF) cytokines. Detailed identification of species, especially mycoplasmata, was tried to improve our understanding of the pathogenesis of PL. Method of study AF from 20 women with PL and 20 controls were evaluated. Infection was detected by PCR for Mycoplasma hominis, Ureaplasma urealyticum and 16S rRNA bacterial gene, which was cloned and sequenced for bacterial identification. Interleukin (IL)-1b, IL-6, IL-8 and tumor necrosis factor (TNF)-a levels were measured by ELISA. Results Frequency of intra-amniotic infection is higher in PL (40.0%). Sequencing-based method identified Bacteroides fragilis, Prevotella bivia and Leptotrichia amnionii, in addition to Mycoplasma species detected by PCR. AF infection correlated with increased IL-1b and IL-6 levels. Conclusion The frequency of intra-amniotic infection, especially M. hominis, in PL women who delivered with 7 days, is high and correlates with high IL-1b and IL-6 levels, but not IL-8.
Reproductive Biology and Endocrinology, 2007
Background Chorioamniotic membranes infection is a pathologic condition in which an abnormal secretion of proinflammatory cytokines halts fetal immune tolerance. The aim of the present study was to evaluate the functional response of human chorioamniotic membranes, as well as the individual contribution of the amnion and choriodecidua after stimulation with Escherichia coli, a pathogen associated with preterm labor. Methods Explants of chorioamniotic membranes from 10 women (37–40 weeks of gestation) were mounted and cultured in a Transwell system, which allowed us to test the amnion and choriodecidua compartments independently. Escherichia coli (1 × 10 6 CFU/mL) was added to either the amniotic or the choriodecidual regions or both; after a 24-h incubation, the secretion of IL-1beta, IL-6, TNFalpha, IL-8, and IL-10 in both compartments was measured using a specific ELISA. Data were analyzed by Kruskal-Wallis one-way analysis of variance. Results After stimulation with Escherichia coli, the choriodecidua compartment showed an increase in the secretion of IL-1beta (21-fold), IL-6 (2-fold), IL-8 (6-fold), and IL-10 (37-fold), regardless of which side of the membrane was stimulated; TNFalpha secretion augmented (22-fold) also but only when the stimulus was applied simultaneously to both sides. When the amnion was stimulated directly, the level of IL-1beta (13-fold) rose significantly; however, the increase in IL-8 secretion was larger (20-fold), regardless of the primary site of infection. TNFalpha secretion in the amnion compartment rose markedly only when Escherichia coli was simultaneously applied to both sides. Conclusion Selective stimulation of fetal membranes with Escherichia coli results in a differential production of IL-1beta, IL-6, TNFalpha, IL-8, and IL-10. These tissues were less responsive when the amnion side was stimulated. This is in agreement with the hypothesis that the choriodecidua may play a primary role during an ascending intrauterine infection, being the main barrier to progression of the infection into the amniotic cavity. Therefore, the tissue-specific capacities for the secretion of these immune modulators could be a determining factor for the degree of severity of the inflammation process in fetal membranes.
Journal of Maternal-fetal & Neonatal Medicine, 2003
Background/objective: Fetal inflammatory response has been implicated as a mechanism of multi-system organ injury in preterm and term neonates. Microbial invasion of the amniotic cavity (MIAC) is frequently associated with a fetal inflammatory response. However, there are no studies comparing the fetal response to MIAC in term and preterm gestations. The purpose of this study was to compare the umbilical cord plasma interleukin-6 (IL-6) concentrations in term and preterm neonates in the presence or absence of MIAC. Study design: Umbilical cord blood was obtained at birth from 252 neonates whose mothers had an amniocentesis within 48 h of delivery (preterm delivery, n = 62; term delivery, n = 190). MIAC was defined as a positive amniotic fluid culture for bacteria or genital mycoplasmas. IL-6 was measured by a sensitive and specific immunoassay. Results: The median IL-6 concentration in umbilical cord plasma was significantly higher in preterm neonates than in term neonates (median 13.4 pg/ml, range 0.1-676 pg/ml vs. median 3.2 pg/ml, range 0.1-408 pg/ml; p < 0.0001). In the context of MIAC, the median umbilical cord plasma IL-6 concentration was significantly higher in preterm than in term neonates (median 31.6 pg/ml, range 1.4-676 pg/ml vs. median 11.7 pg/ml, range 1.3-82 pg/ml, respectively; p < 0.05). Neonates born to mothers with a positive amniotic fluid culture had a significantly higher median IL-6 concentration than neonates born to mothers with a negative amniotic fluid culture (preterm: median 31.6, range 1.4-676 pg/ml vs. median 8.0, range 0.1-656 pg/ml; p < 0.05 and term: median 11.7, range 1.3-82 pg/ml vs. median 3.1, range 0.1-408 pg/ml; p < 0.01, respectively). Conclusions: The preterm fetus is capable of mounting a systemic cytokine response as measured by IL-6 in its peripheral blood. In the setting of MIAC, a fetal IL-6 response is higher in preterm than in term gestation. J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by 118.174.28.35 on 05/20/14 For personal use only. 33 Cord blood IL-6 in preterm and term neonates Yoon et al. J ournal of Mater nal-Fetal and Neonatal Medicin e J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by 118.174.28.35 on 05/20/14 For personal use only. Cord blood IL-6 in preterm and term neonates Yoon et al. J ournal of Maternal-Fetal and Neonatal Medicin e 36 J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by 118.174.28.35 on 05/20/14 For personal use only. Cord blood IL-6 in preterm and term neonates Yoon et al. J ournal of Mater nal-Fetal and Neonatal Medicin e J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by 118.174.28.35 on 05/20/14
Amniotic fluid interleukin 6 in preterm labor. Association with infection
Journal of Clinical Investigation, 1990
To evaluate whether IL-6 participates in the host response to intrauterine infection, we studied IL-6 bioactivity and isoforms in amniotic fluid (AF). Two different assays for IL-6 were used: the hepatocyte stimulating factor assay (in Hep3B2 cells) and the SDS-PAGE/immunoblot assay. IL-6 determinations were performed in 205 AF samples. Samples were obtained from patients in the midtrimester of pregnancy (n = 25), at term with no labor (n = 31), at term in active labor (n = 40), and from patients in preterm labor (n = 109). Higher AF IL-6 levels were observed in women in preterm labor with intraamniotic infection than in women in preterm labor without intraamniotic infection (median = 375 ng/ml, range = 30-5000 ng/ml vs. median = 1.5 ng/ml, range = 0-500, respectively, P < 0.0001). The 23-25and 28-30-kD IL-6 species could be readily detected in SDS-PAGE immunoblots performed directly on 10-,ul aliquots of AF from patients with intraamniotic infection. Among women in preterm labor with culture-negative AF, those who failed to respond to subsequent tocolytic treatment had higher AF IL-6 concentrations than those who responded to therapy (median = 50 ng/ml vs. median = 1.2 ng/ml, respectively, P < 0.05). Only low levels of IL-6 were detected in AF obtained from normal women in the midtrimester and third trimester of pregnancy. Decidual tissue explants obtained from the placentas of women undergoing elective cesarean section at term without labor (n = 11) produced IL-6 in response to bacterial endotoxin. In a pilot study, AF IL-6 was determined in 56 consecutive women admitted with preterm labor. All patients (n = 10) with elevated AF IL-6 (cutoff = 46 ng/ml) delivered a premature neonate. 4 of these 10 patients had positive AF cultures for microorganisms. These studies implicate IL-6 in the host response to intrauterine infection and suggest that evaluation of AF IL-6 levels may have diagnostic and prognostic value in the management of women in preterm labor. (J.
Microbiological characteristics and inflammatory cytokines associated with preterm labor
Archives of Gynecology and Obstetrics, 2011
Purpose To evaluate vaginal microXora and interleukin-1 (IL-), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-) concentrations in the cervicovaginal Xuid of a group of pregnant women in preterm labor when compared with a group of full-term pregnant women not yet in labor. Method Case-control study performed in a University tertiary referral maternity in Campinas, Brazil with 45 pregnant women in preterm labor and 45 full-term pregnant women not in labor. All patients underwent speculum examination for the collection of cervicovaginal Xuid. Bacterial vaginosis (BV) was diagnosed according to the criteria of Amsel and Nugent. Culture was performed for group B streptococcus (GBS) and lactobacilli, and hybrid capture assay for screening for chlamydial and gonococcal infection. Cytokine concentrations were measured using ELISA technique. Statistical analysis was performed using 2 , Fisher's exact, and crude and adjusted odds ratios. SigniWcance level was deWned at 5%. The main outcome measures were cervicovaginal cytokines in preterm labor. Results IL-6 and IL-8 were signiWcantly associated with preterm labor. The changes in vaginal microXora, as well as BV and GBS, were more frequent in women in preterm labor, although BV and GBS showed no statistical signiWcance. The presence of Candida sp., absence of lactobacilli, positive screening for chlamydial and gonococcal infection and the presence of IL-1 and TNF-were not associated with preterm labor. Conclusions IL-6 and IL-8 and the presence of any type of vaginal infection were the factors that were signiWcantly associated with preterm labor.
Clinics in Perinatology, 1995
Prematurity is the leading cause of perinatal morbidity and mortality worldwide, 295 affecting 5% to 10% of births. Preterm neonates have a 120-times higher risk of death than term neonates, 136 • 157 • 269 and survivors are at risk for short-term and long-term morbidity, which includes bronchopulmonary dysplasia, blindness, and psychomotor retardation. 2 • 9, 26 • 70 • 118 • 169 The prevention of premature birth is the single most important challenge to modem obstetrics today. Progress in this area has been hampered by lack of understanding of the basic mechanisms responsible for premature labor and delivery. A growing body of evidence suggests that infection plays a key role in the pathogenesis of preterm labor and delivery. This article reviews this evidence and the proposed mechanisms by which infection leads to preterm parturition. Three lines of evidence support a role for infection in the onset of preterm labor: (1) the administration of bacteria or bacterial products to
mBio, 2011
The fetal response to intrauterine inflammatory stimuli appears to contribute to the onset of preterm labor as well as fetal injury, especially affecting newborns of extremely low gestational age. To investigate the role of placental colonization by specific groups of microorganisms in the development of inflammatory responses present at birth, we analyzed 25 protein biomarkers in dry blood spots obtained from 527 newborns delivered by Caesarean section in the 23rd to 27th gestation weeks. Bacteria were detected in placentas and characterized by culture techniques. Odds ratios for having protein concentrations in the top quartile for gestation age for individual and groups of microorganisms were calculated. Mixed bacterial vaginosis (BV) organisms were associated with a proinflammatory pattern similar to those of infectious facultative anaerobes. Prevotella and Gardnerella species, anaerobic streptococci, peptostreptococci, and genital mycoplasmas each appeared to be associated with...