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

Am J Obstet Gynecol. 1999 Feb;180(2 Pt 1):429-34. doi: 10.1016/s0002-9378(99)70227-9.


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 20-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 1alpha, interleukin 1beta, 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 alpha 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 1alpha, interleukin 1beta, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytokines / biosynthesis*
  • Escherichia coli Infections / immunology*
  • Female
  • Fetus / immunology*
  • Gestational Age
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Kinetics
  • Mice
  • Obstetric Labor, Premature / microbiology*
  • Placenta / immunology
  • Pregnancy
  • Pregnancy Complications, Infectious / immunology
  • Pregnancy Complications, Infectious / microbiology*
  • Sialoglycoproteins / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Uterine Diseases / immunology
  • Uterine Diseases / microbiology*
  • Uterus / immunology


  • Cytokines
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-6
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha