INCREASED ACTIVITY OF INTERLEUKIN-6 BUT NOT TUMOR-NECROSIS-FACTOR-ALPHA IN LUNG LAVAGE OF PREMATURE-INFANTS IS ASSOCIATED WITH THE DEVELOPMENT OF BRONCHOPULMONARY DYSPLASIA

Although considerable evidence suggests that bronchopulmonary dysplasi a (BPD) is the result of prolonged inflammation and impaired healing o f the immature lung, the mediators that regulate inflammation in neona tal lung injury have not been completely elucidated. We examined wheth er the cytokines IL-6 and tumor necrosis factor-alpha(TNF) interact to modulate a cascade of cell-cell signaling events involved in inflamma tion contributing to the development of BPD. To determine the relative activities of these cytokines in neonatal lung injury, lung lavage sa mples were serially obtained from 1 to 28 d from 11 infants with self- limited respiratory distress syndrome (RDS), 19 infants with evolving BPD, and 10 control infants ventilated for nonpulmonary reasons. On th e first day of life, there were no differences in antigenic IL-6 conce ntrations in lavage fluids among the BPD, RDS, and control groups, but IL-6 activity determined by the 7TD1 proliferation assay was 15-fold and 6.6-fold higher in lung lavage of infants who developed BPD compar ed with activities in lavage from control and RDS infants, respectivel y (control, 49.4 +/- 17.6; RDS, 117.3 +/- 59.6; BPD, 779.5 +/- 212.6 x 10(3) hybridoma units/L, mean +/- SEM,p = 0.02). This suggests that p athways for inactivating or inhibiting IL-6 that may be present in the lungs of RDS and control infants may be deficient in BPD infants. IL- 6 activity remained elevated in lavage of BPD infants for the first 2 wk and declined to low levels by d 28. There were no differences among groups on the first day of life for TNF antigen concentration or TNF activity determined by the L929 bioassay. Detectable but low TNF activ ity was found in BPD samples, with peak activity found in d-14 samples . Differences in complex interactions among these and other cytokines with their receptors and inhibitors may predispose some infants with R DS to develop BPD.