Inhibition of cyclooxygenase-2 prevents inflammation-mediated preterm labor in the mouse

Prostaglandins (PGs) have proven important during parturition, but inhibiti on of PG production treating preterm labor (PTL) results in significant mat ernal and fetal side effects. We hypothesize that specific inhibition of ei ther cyclooxygenase (COX)-1 or -2 may result in separation of therapeutic a nd toxic effects. We demonstrate that COX-2, but not COX-1, is induced duri ng inflammation-mediated PTL caused by lipopolysaccharide (LPS) administrat ion. A two-to threefold increase in uterine and ovarian PG concentrations c oincides with this induction of COX-2. The COX-2-selective inhibitor SC-236 proved effective in stopping preterm delivery and the increases in PGs. Th e COX-1-selective inhibitor SC-560 also attenuated uterine and ovarian PG p roduction after LPS but did not inhibit PTL as efficiently as SC-236. COX-1 -deficient mice, which show delay in the onset of term labor, exhibited no delay in onset of PTL after LPS. These findings suggest that the mechanisms for initiation of inflammation-mediated PTL and term labor differ and that selective COX-2 inhibition may provide a means of stopping inflammation-in duced PTL in humans.