Article Text

LIPOPOLYSACCHARIDE-BINDING PROTEIN, SOLUBLE CD14, AND INFLAMMATORY CYTOKINE PRODUCTION AMONG TERM AND PRETERM PREGNANCIES EXPOSED TO CLINICAL CHORIOAMNIONITIS
  1. E M Speer1,
  2. D A Gentile2,
  3. A Patel2,
  4. D P Skoner2
  1. 1Department of Pediatrics, University of Chicago, Chicago, IL, USA
  2. 2Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA, USA

Abstract

Objective Intrauterine infections and the resulting maternal and fetal inflammatory response have been recognized as contributors to morbidity and mortality, especially among preterm infants. Bacterial endotoxin binds to lipopolysaccharide-binding protein (LBP) and CD14. The interaction of endotoxin-LBP-CD14 complexes with toll-like and others receptors leads to production of inflammatory cytokines. We examined the relationship between cytokines, LBP and CD14 among term and preterm pregnancies with or without clinical chorioamnionitis.

Methods We measured cytokine concentrations (IL-1b, IL-6, IL-8, IL-10, IL-12p40, TNFa) in maternal postpartum plasma and supernatants from LPS-stimulated cord blood mononuclear cells from 44 preterm (24–36 weeks gestation) and 52 term newborns (37–42 weeks) with Luminex multiplexing. LBP and soluble CD14 (sCD14) in maternal and cord plasma were measured with ELISA. We diagnosed clinical chorioamnionitis using Gibbs criteria, and defined significance as p<0.05.

Results Plasma concentrations of fetal LBP versus fetal sCD14 and maternal LBP versus maternal sCD14 correlated significantly (Spearman correlation  =  +0.46, p<0.001 and +0.33, p = 0.001, respectively). Fetal LBP correlated significantly with maternal IL-6 and IL-8 and fetal sCD14 with maternal IL-6 and maternal LBP, but not with fetal cytokines. Among chorioamnionitis cases (n = 16, of these 12 were preterm), maternal IL-6 and IL-8 and fetal LBP and sCD14 were significantly elevated compared to non-exposed cases.

Conclusions Previous reports have shown that elevated sCD14 and LBP can promote pro-inflammatory immunity, especially in the extravascular compartment. Our findings suggest an association between clinical chorioamnionitis, fetal LBP and sCD14 and maternal inflammatory cytokines, which in turn might predispose these newborns to pathological inflammatory conditions.

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