Faculty Bibliography

PROBLEM/OBJECTIVE:Intra-uterine infections increase production of pro-inflammatory cytokines. It is unclear whether different infectious agents determine the relative expression of pro-and anti-inflammatory cytokines. METHODS OF STUDY/METHODS:We compared the placental inflammatory response induced by bacterial lipopolysaccharide (LPS, endotoxin from Gram-negative bacteria) with those induced by lipoteichoic acid (LTA, a cell wall component of Gram-positive bacteria). Placental explants from term delivery were treated with either LPS or LTA, in the presence or absence of IL-10, for 24 hrs. Cytokines, prostaglandin E(2) (PGE(2)) production and cyclo-oxygenase-2 (COX-2) expression were quantified. RESULTS:Both LTA and LPS significantly induced several cytokines with LPS eliciting more potent effects. IL-6 and IL-8 were induced to comparable levels in response to both LTA and LPS whereas monocyte chemotactic protein-1 (MCP-1) production was induced more by LTA, demonstrating a differential placental response to a specific toll-like receptor (TLR) ligand. IL-10 treatment significantly reduced most pro-inflammatory cytokines as well as PGE(2) induced by both LPS and LTA. Interestingly, IL-10 down-regulated LTA-mediated MCP1 induction, but not that mediated by LPS. Moreover, IL-10 was more effective in down-regulating PGE(2) after LPS- when compared with LTA stimulation. CONCLUSIONS:Our results demonstrate that placental exposure to LTA and LPS appear to trigger distinct cytokine responses that can be modulated by IL-10.

OBJECTIVE: The objective of this study was to determine whether an expanded amniotic fluid cytokine profile predicts spontaneous preterm birth in patients with short cervix in the midtrimester. STUDY DESIGN: Amniocentesis was performed on singleton gestations between 16-24 weeks with a cervical length <or=25 mm. Amniotic fluid from patients who received no surgical or hormonal treatment was assayed for 25 cytokines. Univariate analysis identified cytokine(s) that correlated with the interval between amniocentesis to delivery. Stepwise regression identified which cytokine(s) was most predictive of delivery, followed by the generation of receiver-operator characteristic curves. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Forty-four amniotic fluid samples were analyzed. After stepwise regression, only monocyte chemotactic protein-1 remained significant and was the most predictive of early delivery. With a cutoff of 1320 pg/mL, monocyte chemotactic protein-1 had a 69% sensitivity, 83% specificity, 36% positive predictive value, and 87% negative predictive value to predict spontaneous preterm birth within 1 week of amniocentesis (P = .015). CONCLUSION: Among 25 cytokines, monocyte chemotactic protein-1 was most predictive of spontaneous preterm birth

OBJECTIVE: We sought to determine the relationship between the degree of cervical shortening and intraamniotic inflammation in patients presenting with a midtrimester short cervix. STUDY DESIGN: Amniocentesis was performed on singleton pregnancies between 16-24 weeks' gestation with a sonographic cervical length (CL) 1500 pg/mL, CL of 5 mm had an 86% sensitivity, 85% specificity, 58% positive predictive value, and 96% negative predictive value to predict elevated MCP-1 levels. After excluding patients with intraamniotic infection or labor, findings were similar. CONCLUSION: CL