INDUCTION OF INTERLEUKIN-1 RECEPTOR ANTAGONIST IN RHESUS-MONKEYS AFTER INTRAAMNIOTIC INFECTION WITH GROUP-B STREPTOCOCCI OR INTERLEUKIN-1 INFUSION

OBJECTIVE: Interleukin-1 receptor antagonist is a natural inhibitor of interleukin-1, a cytokine implicated in the initiation of preterm lab or after intraamniotic infection. The effects of intraamniotic infecti on and interleukin-1 infusion on the appearance of interleukin-1 recep tor antagonist in amniotic fluid and fetal and maternal plasma were as sessed with a monkey model. STUDY DESIGN: On day 130 of pregnancy four chronically catheterized rhesus macaques received intraamniotic inocu lations of group B streptococci, three monkeys received intraamniotic infusions of recombinant human interlukin-1 beta, and three monkeys re ceived buffered saline solution infusions. At timed intervals samples of amniotic fluid, fetal plasma, and maternal plasma were assayed for interleukin-1 beta and interleukin-1 receptor antagonist by immunoassa ys. Uterine activity was continuously monitored by intraamniotic press ure catheters and by electromyographic activity. RESULTS: Interleukin- 1 receptor antagonist, but not interleukin-1 beta, was present in the amniotic fluids of all monkeys before intervention. Infection induced the appearance of interleukin-1 beta and an increase in interleukin-1 receptor antagonist in the amniotic fluid. Interleukin-1 beta infusion resulted in a similar increase in the intraamniotic concentration of interleukin-1 receptor antagonist. Both infection and interleukin-1 be ta infusion were followed by the transient appearance of interleukin-1 receptor antagonist in the plasma of all fetuses. The subsequent decr ease in plasma levels was paralleled by increased amniotic fluid level s of interleukin-1 receptor antagonist. Interleukin-1 beta and interle ukin-1 receptor antagonist were not detected in maternal plasma. Both infection and interleukin-1 infusion induced preterm labor in all trea ted animals. CONCLUSIONS: Interleukin-1 receptor antagonist is a norma l component of monkey amniotic fluid. Intraamniotic infection or the a ppearance of interleukin-1 beta in the amniotic fluid results in incre ased production of interleukin-1 receptor antagonist. Under physiologi c conditions interleukin-1 receptor antagonist in amniotic fluid may i nhibit interleukin-1-induced preterm labor.