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 μg of recombinant human IL-1β (rhIL-1β) or 105-108 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-1β 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 overrexpression 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 laboar in this model does not depend on IL-1 signaling alone.
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