Induction of necrotizing funisitis by fetal administration of intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin in premature fetal sheep

The purpose of the present study was to determine whether experimental intrauterine inflammation could induce necrotizing funisitis, a severe, chronic inflammation of the umbilical cord. Fetuses, randomly divided into four groups (n = 4 each), were infused with 50 μg/d of granulocyte-colony stimulating factor (G-CSF) intravenously on d 125-129 of gestation (G-CSF group), 20 mg of endotoxin into the amniotic cavity on d 127 gestation (endotoxin group), both G-CSF and endotoxin (G-CSF + endotoxin group), or only saline (control group). On d 130 of gestation, the umbilical cords were processed for histologic analysis, scored for degree of inflammation, and compared statistically. At birth, the blood polymorphonuclear leukocyte counts in G-CSF and G-CSF + endotoxin groups were significantly higher than those in endotoxin and control groups (p < 0.05). The inflammatory score of the umbilical cord in G-CSF + endotoxin group was significantly higher than those in the other three groups (p < 0.05). All the fetuses in G-CSF + endotoxin group had necrotizing funisitis, but none of the fetuses in the other three groups developed this condition. An increase in blood polymorphonuclear leukocytes before their activation in the umbilical cord is probably essential for experimentally inducing necrotizing funisitis.