The effect of a matrix metalloproteinase inhibitor on inflammation-mediated preterm delivery.
OBJECTIVE
Several matrix metalloproteinases (MMP) have been implicated in preterm parturition. We hypothesized that administration of a MMP inhibitor would reduce the rate of inflammation-mediated preterm delivery and prolong gestation in a mouse model.


METHODS
We utilized an animal model of endotoxin-induced preterm delivery using timed pregnant C57Bl6 mice. Test animals received lipopolysaccharide (LPS) followed by the MMP inhibitor at 1 dose 12 hours after the LPS. Control mice received the same dose of LPS, followed by a control solution 12 hours after the LPS. The primary outcome was preterm delivery rate.


RESULTS
Mice in the study group had a significantly lower rate of preterm delivery (44%) compared to 100% in the controls (P = .009). Furthermore, the latency between the administration of injection and delivery was also longer in the study group (means 28.3 hours, standard deviation 9.4 hours) than among controls (mean 15.7 hours, standard deviation 1.8 hours) (P < .001).


CONCLUSIONS
Administration of an MMP inhibitor results in a decreased rate of inflammation-mediated preterm delivery in this animal model.
Koscica
Karen L
KL
Department of Obstetrics and Gynecology, Newark Beth Israel Medical Center, Newark, NJ, USA.
Ananth
Cande V
CV
Placido
Jessica
J
Reznik
Sandra E
SE
D000818:Animals; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D007274:Injections, Intraperitoneal; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011480:Protease Inhibitors / Q000494:pharmacology*; D013997:Time Factors
D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors