Downregulatory cytokines in tracheobronchial aspirate fluid from infants with chronic lung disease of prematurity.

UNLABELLED: Chronic lung disease of prematurity (CLD) is associated with an inflammatory response in the preterm lung and increased levels of proinflammatory cytokines in tracheobronchial aspirate fluid (TAF). We investigated TAF levels of transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), interleukin-4 (IL-4) and interleukin-12 (IL-12) cytokines possibly important in downregulating the proinflammatory response and/or inducing lung fibrosis in infants with developing and established CLD. Infants with CLD (n = 24) were compared with preterm infants with RDS that resolved (n = 22) and postoperative infants without lung disease (n = 23). TAF levels of TGF-beta1, IL-10, IL-4 and IL-12 were studied by quantitative enzyme immunoassay. Levels of TGF-beta1 were significantly higher during the first week of life in infants who developed CLD, remained high at 2 wk and past 4 wk of age. TAF levels of TGF-beta1 did not decrease significantly in six infants with CLD after treatment with steroids. TAF IL-10 was detected in 12/46 (26%) preterm infants. Infants with CLD or RDS were more likely to have measurable TAF levels of IL-10, compared with the postoperative infants without lung disease (p < 0.02 and 0.04, respectively). TAF levels of IL-4 or IL-12 were below the detection limits in all samples.

CONCLUSIONS

We have demonstrated a sustained increase of TGF-beta1 levels in TAF from preterm infants who develop CLD, suggesting an important role for TGF-beta1 in the fibrotic response in the CLD lung. The elevated TGF-beta1 levels, combined with an absent or irregular secretion of IL-4, IL-10 and IL-12, can have importance for the increased tendency for the development of CLD in preterm infants.