Effect of stimulation and antagonism of interleukin-1 signaling on preterm delivery in mice

J Soc Gynecol Investig. 2005 Oct;12(7):533-8. doi: 10.1016/j.jsgi.2005.06.006.

Abstract

Objective: Transgenic mice that overexpress the interleukin-1 receptor antagonist (IL-1ra), an endogenous competitive inhibitor of interleukin-1 (IL-1) signaling, were used to test whether blockade of IL-1 can prevent bacterially induced preterm delivery in a validated murine model. These IL-1ra transgenic mice have been shown previously to be protected from lethal endotoxin shock.

Methods: In a series of four separate experiments, 201 female wild-type and transgenic mice on day 14.5 of a 19-20 day gestation underwent intrauterine injection with either 0.5-20 microg of recombinant human IL-1beta (rhIL-1beta) or 10(5)-10(8) heat-killed Escherichia coli organisms. Fetuses were either all wild-type, all transgenic, or of mixed genotype (see below). Preterm delivery and maternal survival rates were recorded. IL-1ra protein levels were determined by enzyme-linked immunosorbent assay (ELISA).

Results: Intrauterine administration of IL-1beta induced preterm delivery in a dose-dependent manner and did not cause other adverse maternal effects. In bacterially inoculated mice, neither maternal nor fetal carriage of the IL-1ra overexpression transgene affected preterm delivery rates. Fetal carriage of the IL-1ra transgene did not up-regulate IL-1ra protein levels in maternal or fetal tissues.

Conclusion: Although intrauterine IL-1 exposure is sufficient for induction of preterm delivery, it was not possible to prevent bacterially induced preterm birth using the IL-1ra transgene. This may be either because the timing or magnitude of IL-1ra up-regulation in transgenic mice was insufficient to block IL-1's interaction with its receptor, or because bacterially induced labor in this model does not depend on IL-1 signaling alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Escherichia coli / pathogenicity
  • Escherichia coli Infections / complications
  • Female
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pregnancy
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / genetics*
  • Signal Transduction

Substances

  • Interleukin-1
  • Receptors, Interleukin-1