Abstract 1096 Poster Session IV, Tuesday, 5/4 (poster 293)

Intraamniotic infection is associated with premature labor and with decreased incidence of respiratory distress syndrome in infants born prematurely. We have previously shown that intraamniotic IL-1 accelerates surfactant protein and lipid synthesis and improves lung stability in fetal rabbits (J Clin Invest 1997;99:2992-9). In many cases of premature labor, gram-negative bacteria and endotoxin are present in amniotic fluid.

Hypothesis. We hypothesized that endotoxin in amniotic fluid causes premature labor and accelerates lung maturation in fetal rabbits.

Methods. On day 23 or 25 of gestation (term 31), LPS (E. coli 026:B6) at a dose ranging from 0.05 to 500 µg/fetus was injected into the amniotic fluid sacs in one uterine horn of New Zealand White rabbits whereas the contralateral amniotic sacs were injected with vehicle. The does were observed for signs of premature labor. The fetuses were delivered 48 h after the injections. White cells were counted and TNF-alpha levels measured by ELISA in amniotic fluid and bronchoalveolar lavage (BAL). Surfactant protein (SP) A and B mRNA expression in the lungs was measured by Northern blotting. Quasi-static pressure-volume curves were recorded in the range 0 to 30 cmH20 at 5 cmH2O pressure intervals. Lungs were fixed intrabronchially with buffered 4% paraformaldehyde while maintaining a constant 20 cmH2O transpulmonary pressure for 24 h. Lung volumes were then measured by volume displacement and lungs processed for histological studies.

Results. 1) LPS at high doses (50-500 µg/fetus) induced premature labor within 20 hours of administration. 2) In fetuses treated with LPS (5 µg), white cell counts in amniotic fluid and BAL were 3.2- and 9.9-fold higher, respectively, than in control fetuses. TNF concentrations in these fluids were not different between groups 48 h after treatment. 3) Fetal weights and lungs weights were not affected by LPS. Lung volume was 1.4±0.3 ml in controls and 2.4±0.4 ml in LPS-treated fetuses (mean±SE, p=0.03). 4) SP-A and SP-B mRNA expression in LPS-treated lungs were increased 2.3-fold (p=0.02) and 1.4-fold (p=0.04), respectively. 5) Lungs from LPS-treated animals showed a better and more homogenous aeration than control lungs. 6) Static lung compliance was better in animals treated with LPS, as indicated by 2.2- to 2.9-fold greater mean air volume per unit body weight throughout the deflation limb of quasi-static pressure-volume curves (p=0.01).

Conclusions. Intraamniotic administration of LPS to rabbits causes premature labor and accelerates fetal lung maturation as evidenced by increased expression of surfactant protein A and B mRNA's and by improved lung stability. Long-term effects on the lung of prenatal exposure to inflammation remain to be studied.