A Randomized Controlled Trial of Interleukin-1 ReceptorAntagonist in a Rabbit Model of Ascending Infection in Pregnancy

[摘要] Objective:To determinewhether treatment with interleukin-1 receptor antagonist (IL1-ra) would affect amnioticfluid concentrations of tumor necrosis factor alpha (TNF-α) and prostaglandins or clinical or microbiological outcomesin a model of ascending bacterial infection in pregnancy.Methods:Timed pregnant New Zealand white rabbits at 70% of gestation underwent endoscopic inoculation ofthe cervices with106–107cfu Escherichia coli. Animals were randomly assigned in a blinded manner to a 5-h intravenousinfusion of human IL1-ra (10 mg/kg) or placebo beginning 1 – 2 h after inoculation. Blood was drawn fromthedoes for assay of serum IL1-ra concentration before inoculation, at mid-infusion, after the infusion ended and atnecropsy. At necropsy, temperature and cultures were taken, and aspirated amniotic fluid was pooled for assays ofTNF-α, prostaglandin E2( PGE2) and IL1-ra.Results:Serum IL1-ra concentrations rose to a mean of 2 mg/ml at mid-infusion and fell markedly after the infusionto concentrations barely detectable at necropsy. Between the two groups, there were no significant differences inthe rates of fever or positive cultures or in amniotic fluid concentrations ofPGE2or TNF-α.One unique finding wasthe demonstration that administration of human IL1-ra to the does resulted inmeasurable concentrationsof humanIL1-ra in the amniotic fluid.Conclusions:Treatment with an intravenous infusion of human IL1-ra after cervical inoculation withE. colidid notaffect clinical or microbiological outcomes or amniotic fluid concentrations of TNF-α or PGE2. This experimentprovides the first demonstration of passageof human IL1-ra from the maternal bloodstreamto the amniotic fluid.

[学科分类] 妇产科学