Effective diminution of amniotic prostaglandin production by selective inhibitors of cyclooxygenase type 2

OBJECTIVE: Cyclooxygenase inhibitors are effective tocolytic agents, but significant adverse effects limit their use. We hypothesized that selective inhibitors of the isozyme cyclooxygenase 2 would effectively diminish labor- associated prostaglandin production. STUDY DESIGN: We analyzed cyclooxygenase type 1 and 2 expression in amnion, chorion, decidua, and myometrium from laboring or nonlaboring women and tested the efficacy of selective cyclooxygenase 2 inhibition in diminishing prostaglandin production. RESULTS: The expression of cyclooxygenase 2 in amnion from women in labor, either preterm or at term, was significantly higher than in amnion before labor. In contrast, cyclooxygenase 1 expression was unchanged by labor. The enhanced expression of amniotic cyclooxygenase 2 was associated with increased prostaglandin E₂ levels in laboring women. Amniotic prostaglandin E₂ production was effectively diminished by the selective cyclooxygenase 2 inhibitors SC-236 and NS-398 but not by the cyclooxygenase 1 inhibitor SC- 560. CONCLUSION: Selective inhibitors of cyclooxygenase 2 are effective in diminishing prostaglandin production in vitro and may be useful in prevention of preterm deliveries.