AN EXPERIMENTAL-MODEL FOR INTRAAMNIOTIC INFECTION AND PRETERM LABOR IN RHESUS-MONKEYS

OBJECTIVE: Our purpose was to describe the temporal and quantitative r elationship between intraamniotic infection and preterm labor in a non human primate model. STUDY DESIGN: On day 130 of gestation (term 167 d ays) four chronically instrumented rhesus monkeys (Macaca mulatta) wer e infected with an intraamniotic inoculation of 10(6) colony-forming u nits of group B streptococci. Four additional noninfected monkeys were followed up to spontaneous parturition as controls. Amniotic fluid wa s serially sampled in all monkeys both before and after inoculation fo r bacterial growth, tumor necrosis factor-alpha, interleukin-1 beta, i nterleukin-6, prostaglandin E(2), and prostaglandin F-2 alpha, and ute rine activity was continuously recorded. RESULTS: Increases in uterine contractility occurred 28 hours (range 14 to 40 hours) after inoculat ion and were preceded by increases in amniotic fluid cytokines and pro staglandins. Intraamniotic concentrations of tumor necrosis factor-alp ha, interleukin-6, and interleukin-1 beta all rose dramatically 9, 15, and 18 hours after infection and 10 to 20 hours before increases in u terine contractility. In spontaneous parturition only interleukin-6 co ncentrations rose moderately (from 0.1 to 1.2 ng/ml). Increases in pro staglandin E(2) and prostaglandin F-2 alpha paralleled those of the cy tokines. Peak prostaglandin concentrations in intraamniotic infection exceeded by severalfold concentrations seen in spontaneous parturition (16,046 pg/ml vs 2765 pg/ml for prostaglandin E(2), p < 0.05; and 554 7 pg/ml vs 708 pg/ml for prostaglandin F-2 alpha p < 0.05). In spite o f intraamniotic infection none of the monkeys were febrile or had peri pheral leukocytosis at the onset of labor. CONCLUSION: In the rhesus m onkey, after intraamniotic infection, there is a predictable and seque ntial increase in amniotic fluid tumor necrosis factor-alpha, interleu kin-1 beta, and interleukin-6, followed by increases in prostaglandin E(2) and prostaglandin F-2 alpha. These increases all occur before an increase in uterine contractility and before clinical signs of infecti on. Our data provide evidence for a cause-and-effect relationship betw een intraamniotic infection and preterm labor and support the utility of measuring interleukin-6 or other cytokines in the diagnosis of intr aamniotic infection.