OBJECTIVE: Our purpose was to determine whether interleukin-1 is an important mediator of lipopolysaccharide-induced fetal death and, if so, whether interleukin-1 causes fetal death by inducing prostanoid formation in gestational tissues.

STUDY DESIGN: Pregnant C3H/HeN mice were administered lipopolysaccharide, interleukin-1⍺, interleukin-β, or vehicle on days 11 to 13 of pregnancy. Mice were killed 72 hours later and the fetal status was determined. Some mice were pretreated with anti-interleukin-1-receptor antibodies or indomethacin. Decidual explants were established from treated mice, and supernatants were assayed for interleukin-1β and prostaglandin E₂.

RESULTS: Decidua taken from lipopolysaccharide-treated mice produced significantly increased amounts of interleukin-1β, and pretreatment with anti-interleukin-1-receptor antibodies reduced the proportion of fetal deaths after lipopolysaccharide administration from 100% to 33%. The administration of interleukin-1⍺ caused fetal death in a dose-dependent fashion, and decidua taken from interleukin-1–treated mice produced significantly increased amounts of prostaglandin E₂. However, pretreatment with doses of indomethacin that abrogated decidual prostaglandin E₂ production did not reduce the proportion of fetal death after interleukin-1⍺ administration.

CONCLUSIONS: Interleukin-1 is an important mediator of lipopolysaccharide-induced fetal death and causes fetal death by prostaglandin-independent effects.(Am J Obstet Gynecol 1997;176:544-9.)