Effect of the antenatal administration of celecoxib during the second and third trimesters of pregnancy on prostaglandin, cytokine, and nitric oxide levels in rabbits

OBJECTIVE: The purpose of this study was to examine the effects of celecoxib on prostaglandin, cytokine, and nitric oxide synthesis in the pregnant rabbit. STUDY DESIGN: Pregnant rabbits received celecoxib from 13 to 20 days (celecoxib-A), from 13 to 28 days (celecoxib-B), or vehicle from 13 to 28 days by gavage. Blood and tissue were assayed for prostaglandin, cytokine, and nitric oxide oxidation products. RESULTS: Preterm delivery occurred in 4 of 11 controls, 0 of 9 in celecoxib-A, and 0 of 8 in celecoxib-B. Plasma prostaglandin F-2chi was reduced in both treated groups at 20 days and at delivery in celecoxib-B. Plasma thromboxane B-2 was suppressed in celecoxib-B at 20 days and delivery. Cervical prostaglandin E-2 was increased; uterine and cervical plasma thromboxane B-2 declined in celecoxib-B. Celecoxib administration suppressed plasma nitric oxide oxidation products at delivery and cervical nitric oxide oxidation products in celecoxib-B. Uterine and cervical interleukin-1beta and interleukin-6 were decreased, and uterine tumor necrosis factor-alpha increased in celecoxib-B. CONCLUSION: Further studies are required to evaluate the therapeutic benefits of cyclo-oxygenase-2 inhibitors in the setting of preterm parturition.