THE INDUCTION OF CYCLOOXYGENASE-2 (COX-2) IN INTACT HUMAN AMNION TISSUE BY INTERLEUKIN-4

Infection is a major cause of preterm labor. Amniotic fluid from women in preterm labor associated with intrauterine infection contains incr eased concentrations of cytokines. The mechanism underlying this assoc iation may be a cytokine-mediated stimulation of amnion cell prostagla ndin production. The biosynthesis of prostaglandins from arachidonic a cid is regulated by the enzyme cyclo-oxygenase which exists in two for ms; the constitutive form (COX-1) and the other mitogen inducible (COX -2). The purpose of this study was to evaluate the effect of the cytok ine interleukin-4 (IL-4) on cyclooxygenase activity and PGE(2) product ion in amnion. Amnion tissue was taken at caesarean section from term women not in labor and immediately incubated for 2 hours in media cont aining concentrations of IL-4 ranging from 1 to 100 ng/ml. An increase in both COX-2 enzyme and prostaglandin E(2) (PGE(2)) production was o bserved for all concentrations of IL-4 greater than 25 ng/ml (P < 0.05 , n = 8). No change in COX-1 was observed. Our data suggest that the c ytokine IL-4 may be involved in the pathogenesis of premature labor by inducing COX-2 in amnion tissue resulting in increased production of PGE(2) and subsequent myometrial activity.