Differential fetal and maternal contributions to the cytokine milieu in a murine model of infection-induced preterm birth

OBJECTIVE: The aim of the study was to determine the relative productions by maternal and fetal tissues of proinflammatory and anti-inflammatory cytokines in a murine model of infection-induced preterm delivery. STUDY DESIGN: The right uterine horns of CD-1 female mice at 14.5 days of a 19- to eo-day gestation were inoculated with either sterile media or live Escherichia coli. The concentrations of cytokines within uteri, placentas, membranes, and fetal lower body segments were determined by enzyme-linked immunosorbent assay at various times after inoculation. RESULTS: All infected tissues showed large, time-dependent increases in interleukin 1 alpha, interleukin 1 beta, and interleukin 6. These increases were maximal 13 hours after infection and were highest in uteri (15-60 times levels in uninfected tissues). Increases in tumor necrosis factor a and interleukin 1 receptor antagonist were much smaller (3 to 5 times) and were confined to the uterus. Although the uterus contained the greatest concentrations of interleukin 1 alpha, interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha, fetal bodies and placentas contained the highest levels of interleukin 1 receptor antagonist. CONCLUSIONS: Time-dependent increases in maternal and fetal cytokines occurred after acute bacterial infection in this murine model. The fetus and placenta may be the most significant sources of the anti-inflammatory cytokine interleukin 1 receptor antagonist during pregnancy, whereas the uterus appears to be a more important source of interleukin 1, interleukin 6, and tumor necrosis factor alpha. Interleukin 1 receptor antagonist levels within uteri were insufficiently high to effectively inhibit interleukin 1 activity during infection.