AMNIOTIC-FLUID TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1 IN A RABBIT MODEL OF BACTERIALLY INDUCED PRETERM PREGNANCY LOSS

OBJECTIVE: The objective of this study was to determine whether the cytokines tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-1 beta were,produced in the amniotic fluid of the rabbit after intracervical inoculation with Escherichia coli. STUDY DESIGN: Timed pregnant rabbits on day 21 (70% of gestation) were inoculated with a hysteroscope intracervically with 10(4) to 10(5) colony-forming units Escherichia coli or sterile saline solution. Escherichia coli-inoculated animals (N = 16) were put to death at 4, 8, 12, and 16 hours after inoculation. Control animals (N = 6) were put to death at similar intervals. At death, cultures were taken from endometrium, amniotic fluid, peritoneum, and blood. Amniotic fluid was collected and assayed for tumor necrosis factor bioactivity by a modified fibroblast cytotoxic assay in L929 cells, for interleukin-1 alpha, and interleukin-1beta with a specific radioimmunoassay, and for prostaglandin E2 and prostaglandin F2alpha by radioimmunoassay. RESULTS: Levels of amniotic fluid tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-1 beta were elevated as early as 4 hours after inoculation in some animals and by 12 to 16 hours after inoculation in all. Levels of all three cytokines correlated significantly with time from intracervical inoculation with Escherichia coli (p < 0.05). Levels of amniotic fluid prostaglandin E2 and prostaglandin F2alpha correlated significantly with time from intracervical inoculation with Escherichia coli (p < 0.05). CONCLUSIONS: Levels of tumor necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, prostaglandin E2 and prostaglandin F2alpha are elevated in the amniotic fluid of rabbits after intracervical inoculation with Escherichia coli. Similarity exists between elevations of amniotic fluid cytokines in this model and in cases of intraamniotic infection and preterm labor unresponsive to tocolytics in humans. Modulation of cytokines may offer a strategy for improvement of outcome in this experimental model of infection-induced pregnancy loss.