Interleukin-1 Stimulates Human Uterine Prostaglandin Production Through Induction of Cyclooxygenase-2 Expression

PROBLEM: Uterine infection occurs in as much as 20% of preterm labor and results in increased decidual cytokines. The objective of this study was to examine the effect of interleukin‐1 (IL‐1) and the cyclooxygenase‐2 (COX‐2) inhibitor, NS‐398, on myometrial prostaglandin (PG) production and COX‐2 expression. METHOD OF STUDY: Human uterine myocytes were stimulated with IL‐1 (0–50 ng/mL) over 24 hr. PGE2, PGF2α, and 6‐keto F1α were measured by enzyme‐linked immunosorbent assay. Both COX‐1 and COX‐2 proteins and mRNA were measured by western and northern blot, respectively. RESULTS: IL‐1 increased PG production beginning at 6 hr. COX‐2 protein increased beginning at 4 hr and continued to increase at 24 hr. COX‐2 mRNA increased at 2 hr and peaked at 4 hr. NS‐398 blocked PG production but had no effect on COX‐2 protein or mRNA. CONCLUSIONS: IL‐1 increases PG production by myometrium by increased COX‐2 expression. NS‐398 completely blocks IL‐1‐induced PG production. With intrauterine infection, IL‐1 may induce labor through the autocrine production of uterotonic PGs.