Evaluation of the tocolytic effect of a selective cyclooxygenase-2 inhibitor in a mouse model of lipopolysaccharide-induced preterm delivery

The inflammatory process is known to cause preterm delivery. Recently, a cy clooxygenase (COX)-2 inhibitor has been developed as an anti-inflammatory d rug with few side-effects. We evaluated the COX-2 inhibitor, Celecoxib, for its tocolytic effects and side-effects on darns and pups using a lipopolys accharide (LPS)-induced preterm delivery mouse model (preterm delivery rate s; 95%), With administration of Celecoxib (50, 10, 1 and 0.3 mg/kg), the pr eterm labour rate was significantly reduced to 18, 30, 36 and 60% respectiv ely. The prostaglandin F-2 alpha (PCF2 alpha) and PGE(2) concentrations in murine uterine tissue 4 and 10 h after LPS treatment with Celecoxib (10 and 1 mg/kg) were significantly lower than those in the LPS-treated group with out Celecoxib, With administration of 10 or 100 mg/kg Celecoxib, the fetal ductus arteriosus was constricted significantly in preterm and near-term ra ts, although constriction rates in preterm rats were significantly lower th an those in near-term rats. Reproductive and renal functions in offspring w hose mothers were treated with LPS and Celecoxib were normal. These data de monstrate that Celecoxib could be used as a new therapy for preterm labour. However, careful attention to constriction of the fetal ductus arteriosus should be given.