Amniotic fluid interleukin-6 increase is an indicator of spontaneous preterm birth in white but not black Americans.

Objective: This study examined the differences in the inflammatory cytokine interleukin (IL)-6 and the immunoinhibitory cytokine IL-10 in the amniotic fluid of black and white women in spontaneous preterm birth.

Methods: In this study, 321 amniotic fluids from cases (preterm birth 36 or fewer weeks' gestation) and controls (normal term delivery longer than 37 weeks' gestation) were collected (147 cases [49 blacks and 98 whites] and 174 controls [85 blacks and 89 whites]) at the time of active labor. IL-6 and IL-10 concentrations were measured by immunoassays.

Infection and the role of inflammation in preterm premature rupture of the membranes.

Spontaneous preterm birth, caused by preterm labor (contractions before 37 weeks' gestation) or preterm premature rupture of the membranes (pPROM) (membrane rupture before the onset of labor) or both account for approximately 80% of preterm deliveries. pPROM is associated with 30-40% of preterm deliveries and the incidence of pPROM has increased in the past decade. The question we address here is why some women experience pPROM and some experience preterm labor with no rupture of membranes (ROM) when the etiologic factors associated with both these pathologic complications are the same.

Human fetal membrane expression of IL-19 and IL-20 and its differential effect on inflammatory cytokine production.

Objective. The objectives of this study were to document the expression of IL-19 and IL-20, localize their expression in human fetal membranes and to examine their influence on the production of other inflammatory cytokines (IL-1, IL-6, IL-8, and TNF-alpha) from placental membranes.Methods.

Differences in the placental membrane cytokine response: a possible explanation for the racial disparity in preterm birth.

Problem: The prematurity rate is higher in African-Americans (AA) compared with Caucasians (C). As spontaneous preterm labor has been hypothesized to be a host inflammatory response disease racial differences in human placental membrane inflammatory cytokine and prostaglandin pathway gene expression patterns between AA and C were examined in this report.

Method Of Study: Placental membranes (amniochorion) collected from AA and C women from cesareans at term were maintained in an organ explant system and stimulated with endotoxin (lipopolysaccharide, LPS).

The role of matrix degrading enzymes and apoptosis in rupture of membranes.

Prematurity is the third leading cause of perinatal death, and preterm premature rupture of the membranes (pPROM) is associated with approximately 20-50% of all preterm births. The etiologic factors described for pPROM and preterm labor (PTL) are the same, although the clinical presentation (pPROM vs PTL) differs among patients. The reason for this disparity is unknown and poses a therapeutic dilemma.

Racial disparity in membrane response to infectious stimuli: a possible explanation for observed differences in the incidence of prematurity. Community Award Paper.

Objective: This study compares the immune responsiveness of amniochorionic membranes (AC) derived from African American (AA) and white (C) women to an infectious stimulus ex vivo.

Study Design: AC derived from AA and C women were placed in an organ explant culture for 48 hours and then stimulated with endotoxin. Enzyme-linked immunosorbent assay measured the concentration of matrix metalloproteinase 9 (MMP9), tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptors (sTNFR1 and sTNFR2) in culture media from stimulated and unstimulated AC.

IL-1 beta is a better inducer of apoptosis in human fetal membranes than IL-6.

The objective of this study was to compare two of the inflammatory cytokines (IL-1 and IL-6) elevated in both preterm labour and preterm premature rupture of the membranes (pPROM), with respect to their ability to induce fetal membrane apoptosis. Fetal membranes collected from women at term were placed in an organ explant system and stimulated with recombinant human IL-1 beta and IL-6. The expression patterns of pro-apoptotic genes (Fas, FasL, TRADD, FADD) and caspases 2, 3, 8, 9 were studied using PCR.

Role of tumor necrosis factor-alpha in the premature rupture of membranes and preterm labor pathways.

Objective: To further delineate the differences between the preterm labor and premature rupture of the membrane pathways, we investigated the role of the inflammatory cytokines as activators of matrix metalloproteinases 2 and 9 in human fetal membranes.

Study Design: Normal amniochorionic membrane that is maintained in an organ explant system was stimulated with interleukin-1beta, tumor necrosis factor-alpha, or interleukin-6. The expression and activity of matrix metalloproteinases 2 and 9 in amniochorion was documented with reverse transcriptase-polymerase chain reaction and specific substrate activity assays.

Screening of novel matrix metalloproteinases (MMPs) in human fetal membranes.

Objective: Endogenous activation of matrix metalloproteinase (MMP) in human fetal membranes is hypothesized to contribute to membrane weakening leading to early rupture and is also involved in the initiation of labor. Our laboratory and several others have studied the source and action of some of these MMPs. The objective of this study is to document the expression pattern of most of the MMPs cloned and sequenced so far in amniochorion during preterm premature rupture of membranes (pPROM), at term not in labor and during term labor.

Interleukin-10 inhibition of gelatinases in fetal membranes: therapeutic implications in preterm premature rupture of membranes.

Objective: To examine the effect of interleukin-10 on production and regulation of gelatinases by amniochorion in an in vitro model of infection.

Methods: We placed amniochorionic membranes collected from eight women who had elective repeat cesareans at term in an organ explant culture system. After 48 hours in culture, the membranes were stimulated with lipopolysaccharide (50 ng/mL), and some were costimulated with interleukin-10 (500 ng/mL).

Distinct molecular events suggest different pathways for preterm labor and premature rupture of membranes.

Objective: On a clinical level, the etiologies associated with premature rupture of the membranes and preterm labor are virtually identical, though these conditions end in distinctly different events. This study was designed to determine differences between preterm labor and preterm premature rupture of membranes by using molecular markers of extracellular matrix degradation and apoptosis.

Study Design: Amniochorion and amniotic fluid samples were collected from gestational age-matched groups of women undergoing cesarean delivery before term.

Support for an infection-induced apoptotic pathway in human fetal membranes.

Objective: Lipopolysaccharide and tumor necrosis factor alpha levels are both elevated in the amniotic fluid of women during infection-associated preterm labor and premature rupture of fetal membranes. Our laboratory has shown that apoptosis is associated with premature rupture of fetal membranes but is not associated with preterm labor. The exact pathway that leads to apoptosis-mediated premature rupture of fetal membranes is still unclear.

Programmed cell death (apoptosis) as a possible pathway to metalloproteinase activation and fetal membrane degradation in premature rupture of membranes.

Objective: Increased matrix metalloproteinase 2 expression and activity are associated with premature rupture of fetal membranes. A proapoptotic protein produced in response to deoxyribonucleic acid fragmentation, p53, can bind to the matrix metalloproteinase 2 gene promoter and cause increased gene expression. It promotes apoptosis by inducing the expression of the proapoptotic bax gene and inhibiting the antiapoptotic bcl-2 gene.

Amniochorion gelatinase-gelatinase inhibitor imbalance in vitro: a possible infectious pathway to rupture.

Objective: To estimate the effect of lipopolysaccharide on gelatinases and tissue inhibitors of matrix metalloproteinase 2 (gelatinase inhibitor) balance in human fetal membranes.

Methods: Amniochorionic membranes in organ explant were stimulated with 1000 ng/mL lipopolysaccharide for 24 hours after a 48-hour preincubation period. Quantitative competitive polymerase chain reaction (PCR) was done to quantitate messenger RNAs for gelatinase A and B (matrix metalloproteinase 2 and 9) and tissue inhibitor of metalloproteinase 2.

The effect of transforming growth factor and interleukin-10 on interleukin-8 release by human amniochorion may regulate histologic chorioamnionitis.

Objective: Amniochorion is a source of interleukin-8 during infection and inflammation. In this study we investigate the role of 2 immunoinhibitory cytokines, transforming growth factor and interleukin-10, in regulating interleukin-8 production from human fetal membranes and define their mechanism of regulation.

Study Design: Amniochorion was placed in an organ explant system for 72 hours.