Induction of interleukin-1 receptor antagonist in rhesus monkeys after intraamniotic infection with group B streptococci or interleukin-1 infusion

Abstract

Objective: Interleukin-1 receptor antagonist is a natural inhibitor of interleukin-1, a cytokine implicated in the initiation of preterm labor after intraamniotic infection. The effects of intraamniotic infection and interleukin-1 infusion on the appearance of interleukin-1 receptor antagonist in amniotic fluid and fetal and maternal plasma were assessed with a monkey model.

Study design: On day 130 of pregnancy four chronically catheterized rhesus macaques received intraamniotic inoculations of group B streptococci, three monkeys received intraamniotic infusions of recombinant human interleukin-1 beta, and three monkeys received 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 immunoassays. Uterine activity was continuously monitored by intraamniotic pressure 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 beta infusion were followed by the transient appearance of interleukin-1 receptor antagonist in the plasma of all fetuses. The subsequent decrease in plasma levels was paralleled by increased amniotic fluid levels of interleukin-1 receptor antagonist. Interleukin-1 beta and interleukin-1 receptor antagonist were not detected in maternal plasma. Both infection and interleukin-1 infusion induced preterm labor in all treated animals.

Conclusions: Interleukin-1 receptor antagonist is a normal component of monkey amniotic fluid. Intraamniotic infection or the appearance of interleukin-1 beta in the amniotic fluid results in increased production of interleukin-1 receptor antagonist. Under physiologic conditions interleukin-1 receptor antagonist in amniotic fluid may inhibit interleukin-1-induced preterm labor.