Abstract 222

Amniotic fluid concentrations of proinflammatory cytokines, particularly IL-1, are increased in preterm labor during intraamniotic infections. Infants prenatally exposed to chorioamnionitis are less likely to have respiratory distress syndrome (RDS) than controls. However, after birth, high IL-1 in airway specimens is associated with surfactant dysfunction, and with development of chronic lung disease (CLD). We have shown that intraamniotic of IL-1α (150-1500 ng) promotes maturation of the fetal lung by enhancing the expression of surfactant proteins SP-A and SP-B and improving the dynamic compliance (J Clin Invest 99:2992, 1997).

We hypothesized that the effects of IL-1 are dependent on the degree of maturity.

Methods: Lung explants from fetal (19 to 30 days), newborn and adult rabbits were cultured in the presence of IL-1α (57 to 570 ng/ml). The expression of surfactant protein mRNAs (SP-A, SP-B, SP-C) was studied.

Results: In the explants from immature lung, IL-1α upregulated the expression of SP-A (days 19 and 22) and SP-B (day 22) mRNAs, whereas in mature lung (term fetus, newborn, adult) IL-1α downregulated the expression of surfactant proteins, particularly SP-C. IL-1α did not affect the stability of SP-A mRNA. The effect of IL-1α in enhancing SP-A mRNA was evident within two hours.

Conclusion: IL-1 strikingly increases the expression of SP-A and SP-B in the immature lung. In contrast, it decreases the expression of surfactant proteins in mature lung. This maturity-dependent effect of IL-1 may give an explanation on paradoxical association between IL-1 and the odds of RDS and CLD.