INTERLEUKIN-1-ALPHA UP-REGULATES THE EXPRESSION OF SURFACTANT PROTEIN-A IN RABBIT LUNG EXPLANTS

Interleukin-1 (IL-1) is an important participant in infectious and inf lammatory conditions. Interleukin-1 receptor antagonist (IL-1ra) preve nts the effect of IL-1, We have shown that injection of interleukin-1 alpha (IL-1 alpha) into the amniotic fluid of pregnant rabbits stimula tes the expression of surfactant protein-A (SP-A) in the lungs of the fetuses, We hypothesized that IL-1 alpha similarly enhances the expres sion of SP-A in rabbit lung explants in vitro. Explants obtained from 22-day fetal rabbit lungs were cultured in Waymouth's medium on a rota ting platform in the presence or absence of IL-1 alpha (5.7-570 ng/ml) or IL-1ra (1-10 mu g/ml). Dibutyryl cAMP (1 mM) served as a positive control. After 3 days in culture, the explants were harvested and Nort hern analysis of SP-A was performed using the 1,9-kb rabbit SP-A cDNA probe. IL-1 alpha and dibutyryl cAMP increased the expression of SP-A twofold, as judged by video densitometry. IL-1ra did not change SP-A e xpression as compared with controls, suggesting that endogenous IL-1 a ctivity was not responsible for the basal level of SP-A expression in the explants. Dibutyryl cAMP increased the expression of SP-B mRNA, wh ereas IL-1 alpha had no effect on SP-B mRNA concentration, We conclude that inflammatory mediators interact with lung cells to alter synthes is of important components of the surfactant system.