Amniotic fluid lipopolysaccharide-binding protein and soluble CD14 as mediators of the inflammatory response in preterm labor

OBJECTIVE: Our purpose was to determine the association of lipopolysacchari de-binding protein (LBP) and soluble CD14 (sCD14) with the proinflammatory response among women in preterm labor. The binding of lipopolysaccharide (L PS) with LBP and sCD14 activates macrophages at LPS concentrations up to 10 00 times lower than required with LPS alone. LBP and sCD14 in amniotic flui d could explain the high concentrations of cytokines present in the amnioti c fluid of culture-positive women and the presence of cytokines in the amni otic fluid of culture-negative women. STUDY DESIGN: A cohort of 169 afebrile women in preterm labor with intact m embranes had amniotic fluid collected by transabdominal amniocentesis for c ulture and for LBP, sCD14, and interleukin 6 (IL-6) determinations by enzym e-linked immunosorbent assay. IL-6 levels of >2 ng/mL were considered eleva ted. Statistical analyses included analysis of variance, multiple compariso ns with Bonferroni correction, and linear regression. RESULTS: All 169 amniotic fluid samples had measurable LBP and sCD14. Subje cts were categorized by amniotic fluid culture results and IL-6 concentrati on into 3 groups: (1) positive amniotic fluid culture, (2) negative amnioti c fluid culture, elevated IL-6 concentration, and (3) negative amniotic flu id culture, low IL-6 level. Geometric mean LBP and sCD14 levels differed si gnificantly among groups such that levels were approximately twice as high among pregnancies with positive amniotic fluid culture or elevated IL-6 com pared with those without evidence of inflammation (both P <.001), sCD14 was inversely associated with enrollment gestational age independent of amniot ic fluid culture results and IL-6 concentrations. Among culture negative, l ow IL-6 pregnancies, sCD14 decreased 3.5% for each additional week of gesta tion (95% confidence interval [CI], 0.01%-6.4%; P=.02). LBP levels showed a similar trend in this group (P=.09). One hundred eleven subjects had detec table IL-6 levels. Among these subjects, IL-6 increased by 2.1-fold for eve ry 10-fold increase in LBP (95% CI, 1.1-4.0; P=.02) and by 28.4-fold for ev ery 10-fold increase in sCD14 (95% CI, 10.4-77.4; P <.001) with adjustment for gestational age by linear regression. CONCLUSIONS: LBP and sCD14 are present in amniotic fluid of preterm pregnan cies and are linearly associated with amniotic fluid IL-6 concentrations. T hese molecules may amplify the cytokine response and thereby help explain t he presence of cytokines in amniotic fluid when culturable quantities of mi crobes are absent.