Diversity in cytokine response to bacteria associated with preterm birth by fetal membranes (original) (raw)
Related papers
American Journal of Obstetrics and Gynecology, 1998
Our goal was to evaluate the effect of Escherichia coli, Bacteroides fragilis, Mycoplasma hominis, and Staphylococcus aureus on cytokine and prostaglandin production by amnion cells in vitro. STUDY DESIGN: Amnion cells were obtained from women undergoing elective cesarean section before the onset of labor and cultured in a primary cell culture. Confluent amnion cells were incubated with heat-inactivated bacteria in different concentrations (10 1 to 10 6 colony-forming units/ml) for 48 hours. Samples for quantification of interleukin-1b, interleukin-6, interleukin-8, tumor necrosis factor-a, and prostaglandin E 2 were collected at 6, 12, 24, and 48 hours. RESULTS: Under basal conditions, minor amounts of interleukin-6 and interleukin-8 were detectable. Incubation of amnion cells with E. coli enhanced the secretion of interleukin-8 and also induced an transient increase of prostaglandin E 2 in a dose-dependent manner. B. fragilis produced an increase in the secretion of interleukin-6 and interleukin-8. M. hominis and S. aureus did not cause an increase in either interleukin-6, interleukin-8, or prostaglandin E 2 . CONCLUSION: The gram-negative bacteria E. coli and B. fragilis stimulated interleukin-6 and interleukin-8 to a greater degree than the other bacteria investigated in this study. This finding may be of clinical interest in the onset of preterm birth. (Am J Obstet Gynecol 1998;178:50-3.)
PLoS ONE, 2012
Objective: To compare the inflammatory response preserved ex vivo by decidual cells isolated from women who experienced preterm labor with and without subclinical intrauterine infection. Methods: Fetal membranes were obtained after cesarean section from 35 women who delivered before 37 weeks of gestation following spontaneous preterm labor, with no clinical evidence of intrauterine infection. Decidua was microbiologically tested and cultured. Concentrations of anti-inflammatory cytokines (IL-2, IL-4, IL-10), pro-inflammatory cytokines (IL-6, IL-8, IL-1b and TNF-a), and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9) were measured in the supernatants using Bio-Plex, and prostaglandin E 2 (PGE 2) was measured by enzyme immunoassay. Results: Subclinical infection was confirmed in 10 women (28.5%). Microorganisms isolated were Ureaplasma urealyticum (4), group B streptococci (3), Gardnerella vaginalis (1), and Escherichia coli (2). We found a significant increase of proinflammatory cytokines and a significant decrease of anti-inflammatory cytokines in supernatants from decidual cells obtained from women with preterm labor and subclinical intrauterine infection compared to women without infection. Secretion of MMP-1, MMP-8, MMP-9 and PGE 2 was significantly higher in infected women. Secretion of IL-8 by decidual cells from infected women persisted upon repeated in vitro culture passages. Conclusions: Almost 30% of idiopathic preterm labor cases were associated with subclinical intrauterine infection, and decidual cells isolated from these cases preserved an ex vivo inflammatory status after in vivo bacterial exposure.
European cytokine network, 2007
Our aim was to compare maternal serum concentrations of interleukin(IL)-1alpha IL-1beta, IL-6 and IL-8 in pregnancies complicated by preterm labor (PTL), with the levels in healthy controls at comparable gestational age, and to determine if these assays have any value in the prediction of early-onset neonatal infection or histological chorioamnionitis. The study population consisted of 65 women with new-onset PTL, and 31 healthy controls. Maternal serum concentrations of IL-6 (8.40 versus 3.30 pg/mL; p = 0.002) and IL-1beta (2.20 versus 0.50 pg/mL; p = 0.003) were significantly higher in patients with PTL as compared to healthy pregnant women. The IL-1beta concentration (13.60 versus 1.20 pg/mL; p = 0.02) was significantly higher in the serum of mothers whose babies developed early-onset infections, than in mothers of newborns that were healthy. However, its predictive value, and the value of the other cytokines studied, was poor. In addition, IL-1beta levels (28.79 versus 5.19 pg/m...
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.
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.
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 Interferon & Cytokine Research, 2007
The usefulness of vaginal fluid proinflammatory cytokine assays in the prediction of neonatal congenital infection was evaluated. Sixty-two women between 24 and 34 weeks of pregnancy, complicated by premature rupture of the membranes, were divided into those who delivered newborns with (n ؍ 21) and without (n ؍ 41) signs of infection. Concentrations of all studied cytokines were higher in women who delivered babies with infection. The cutoff values of interleukin-1␣ (IL-1␣) and IL-1 Ն 400, IL-6 Ն 2000, and IL-8 Ն 2100 pg/mL predicted infection with a sensitivity of 57%, 57%, 33%, and 76%, a specificity of 73%, 73%, 93%, and 59%, a positive predictive value of 52%, 52%, 70%, and 48%, and a negative predictive value of 77%, 77%, 73%, and 83%, respectively. Receiver operating characteristic (ROC) curve analysis revealed that the predictive performance of the four studied cytokines was comparable. In conclusion, vaginal fluid cytokines after premature rupture of the membranes have moderately predictive value of whether or not a neonate will develop early sepsis.
Acta Obstetricia et Gynecologica Scandinavica, 2012
To predict microbial invasion of the amniotic cavity (MIAC) and spontaneous preterm delivery within seven days using a panel of selected proteins from amniotic fluid in a Swedish population of preterm prelabor membrane rupture (PPROM). Prospective cohort study. Evaluation of intra-amniotic inflammation in preterm premature rupture of membranes. Sixty-six pregnant women with preterm prelabor membrane rupture at 22(+0) -33(+6) weeks' gestational age. Methods. Twenty-seven amniotic fluid proteins were assayed by a multiple immunoassay. The intra-amniotic inflammatory response was evaluated according to the presence of MIAC and the risk of spontaneous preterm delivery within seven days. A prediction model was constructed using logistic regression. The overall rates of MIAC and spontaneous preterm delivery within seven days were 20 and 50%, respectively. There was a higher inflammatory response in women with MIAC than in those without. Earlier gestational age at delivery and lower birthweight were observed in the presence of microbial invasion of the amniotic cavity. Amniotic fluid interleukin (IL)-6 and IL-10 were the best predictors of MIAC in terms of sensitivity (69%), specificity (81%), positive predictive value (47%), negative predictive value (91%) and a positive likelihood ratio of 3.6. There were no differences in intra-amniotic inflammatory response according to the risk of spontaneous preterm delivery within seven days. Amniotic fluid IL-6 and IL-10 are the best inflammatory biomarkers to predict MIAC in women with PPROM. Intra-amniotic inflammation does not predict the occurrence of spontaneous preterm delivery within seven days of PPROM.
Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor
Pediatric research, 2005
Intrauterine infection has been frequently linked with preterm labor before 30 wk of human pregnancy. Many different species of organisms have been detected, leading to the suggestion that infection-induced preterm labor is a generic inflammatory response to organisms rather than a specific response to a limited number of pathogens. The detection of organisms by microbiological culture is a laborious and unreliable process, so the aim of this study was to harness modern molecular techniques to detect organisms in tissues from human pregnancy. A DNA probe specific for conserved regions of bacterial 16S ribosomal RNA sequence was designed and labeled with fluorescein for fluorescence in situ hybridization. Organisms were detected in the great majority (>80%) of fetal membranes after prolonged premature rupture of the fetal membranes and after preterm labor, which was consistent with previous data. Organisms were also detected in fetal membranes after preterm delivery without labor ...