Amniotic fluid concentrations of several cytokines are increased in preterm labor occurring in the setting of intraamniotic infection. Infants prenatally exposed to chorioamnionitis are less likely to have respiratory distress syndrome than newborns not exposed to intrauterine infection. We have shown that intraamniotic administration of IL-1α promotes maturation of the fetal fung in fetal rabbits by enhancing the expression of surfactant proteins SP-A and SP-B, increasing the recovery of disaturated phosphatidylcholine(DPC) in BAL and improving dynamic compliance of the lungs without decreasing growth of the fetus or of the lungs. Similarly, intraamniotic IL-1α increases surfactant pool size and improves dynamic compliance in fetal lambs.Aim: We hypothesized that intramuscular administration of IL-1α to fetal rabbits would similarly promote maturation of the fetal surfactant system.

Methods: On day 23 of gestation, IL-1α at doses ranging from 0.5 ng/fetus to 1500 ng/fetus was injected i.m. to each fetus in one uterine hom whereas fetuses in the contralateral horn were injected with the saline vehicle. Expression of surfactant proteins, lung weights and DPC and total phospholipid content were analyzed on day 25 of gestation.Results: Mortality of the fetuses was increased at IL-1α doses of 500 ng and especially at 1500 ng. At lower doses, mortality was not affected. At 500 ng/fetus, but not at smaller doses, IL-1α decreased fetal weights (12.6 ± 1.3 g vs. 14.5 ± 0.7 g, p < 0.05). Similarly, DNA content of the right lungs was decreased in animals treated with IL-1α at 500 ng/fetus (560 ± 75 μg vs. 975 ± 120μg), but not at lower doses. The amount of total phospholipid or of DPC in fetal lungs was not increased by intramuscular IL-1α treatment. The expression of surfactant proteins SP-A or SP-B was likewise not affected by intramuscular cytokine injections.

Conclusion: In contrast to intraamniotically administered IL-1α, intramuscular injection of IL-1α does not enhance maturation of the surfactant system but, at high doses, decreases the growth of the fetuses and of their lungs and increases fetal mortality.