Production of interleukin-6 by fetal and maternal cells in vivo during intraamniotic infection and in vitro after stimulation with interleukin-1

Abstract

Amniotic fluid samples were obtained by transabdominal amniocentesis from 20 women in preterm labor (less than or equal to 34 wk gestation). Concentrations of IL-6 in culture-positive amniotic fluids (mean 8706 pg/mL, range 5100-14,446 pg/mL) were higher than those in culture-negative fluids (mean 1133 pg/mL, range 15-6534 pg/mL, p less than 0.0001) or fluids from healthy term pregnancies (mean 196 pg/mL, range less than or equal to 5-790 pg/mL, p less than 0.001). To assess possible sources of the Il-6 in amniotic fluid, we tested the ability of a variety of fetal and maternal cells to produce IL-6 in vitro after stimulation with IL-1, a cytokine known to stimulate IL-6 production. Very low concentrations of IL-6 were present in supernatants of cells not stimulated with IL-1; however, high concentrations were observed in supernatants of stimulated umbilical venous endothelial cells, decidual cells, and fetal and maternal blood mononuclear cells. To determine whether cells from adults produce IL-6 with kinetics similar to those of neonates, we incubated mononuclear cells obtained from blood of adults and term and preterm neonates with IL-1. After 6 h, IL-6 was detected in supernatants of adult cells and term neonatal cells, but not in supernatants of preterm cells. Concentrations at 18, 24, and 48 h were similar for adult and term cell supernatants, but were lower in supernatants of preterm cells. We also observed considerably more IL-6 mRNA accumulation in circulating mononuclear cells from adults than in those from neonates.