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.


CONCLUSIONS
Administration of neutrophil elastase inhibitor might suggest a useful strategy to prevent premature delivery resulting from intrauterine infection.
Department of Obstetrics and Gynecology, Yachiyo Medical Center, Tokyo Womens Medical University, Yachiyo, Chiba, Japan. masaoka@tymc.twmu.ac.jp
Naoki
N
Masaoka
Masao
M
Watanabe
Yoshiyuki
Y
Nakajima
D000818:Animals; D002821:Chorioamnionitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood*; D015232:Dinoprostone / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008070:Lipopolysaccharides; D007752:Obstetric Labor, Premature / Q000209:etiology / Q000517:prevention & control*; D011247:Pregnancy; D011897:Random Allocation; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012756:Sheep; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D014590:Uterine Contraction / Q000187:drug effects*
D016207:Cytokines; D008070:Lipopolysaccharides; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D015232:Dinoprostone; D005998:Glycine