The effects of sivelestat sodium hydrate on uterine contraction and the concentration of maternal and fetal blood cytokines in a sheep model of intra-amniotic infection induced by lipopolysaccharide.

OBJECTIVE: To evaluate the effects of a neutrophil elastase inhibitor, sivelestat sodium hydrate, in a sheep model of intra-amniotic infection(IAI) induced by lipopolysaccharide (LPS) injected into the intra-amniotic compartment. METHODS: We examined 15 chronically instrumented ewes, the ewes were assigned randomly as group A (five ewes) administered an antibiotic after LPS administration, group B (five ewes) administered a neutrophil elastase inhibitor (0.2 mg/kg/h) with an antibiotic after LPS administration, and group C (five ewes) a sham operation group. Uterine contraction was evaluated by fetal tracheal pressure and concentrations of PGE2, IL-6, IL-8, TNF-α in maternal and fetal blood before and after LPS administration were measured chronologically. RESULTS: (1) All ewes of group A delivered within 72 h, but only one ewe of group B delivered. Uterine contraction of group B was suppressed about 60% in comparison with group A. (2) Maternal blood concentrations of PGE2, IL-6, IL-8, and TNF-α level of group A increased chronologically and when compared with groups B and C the increase was significantly higher. (3) There were no significant changes in the fetal blood cytokines in any of the three groups. CONCLUSION: Administration of neutrophil elastase inhibitor might suggest a useful strategy to prevent premature delivery resulting from intrauterine infection.