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 b y maternal and fetal tissues of proinflammatory and anti-inflammatory cytok ines 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 i mmunosorbent assay at various times after inoculation. RESULTS: All infected tissues showed large, time-dependent increases in int erleukin 1 alpha, interleukin 1 beta, and interleukin 6. These increases we re maximal 13 hours after infection and were highest in uteri (15-60 times levels in uninfected tissues). Increases in tumor necrosis factor a and int erleukin 1 receptor antagonist were much smaller (3 to 5 times) and were co nfined to the uterus. Although the uterus contained the greatest concentrat ions of interleukin 1 alpha, interleukin 1 beta, interleukin 6, and tumor n ecrosis factor alpha, fetal bodies and placentas contained the highest leve ls of interleukin 1 receptor antagonist. CONCLUSIONS: Time-dependent increases in maternal and fetal cytokines occur red after acute bacterial infection in this murine model. The fetus and pla centa may be the most significant sources of the anti-inflammatory cytokine interleukin 1 receptor antagonist during pregnancy, whereas the uterus app ears to be a more important source of interleukin 1, interleukin 6, and tum or necrosis factor alpha. Interleukin 1 receptor antagonist levels within u teri were insufficiently high to effectively inhibit interleukin 1 activity during infection.