Transforming growth factor beta (TGFβ) is a peptide implicated in tissue injury and repair but its role in the premature human lung remains unclear. TGFβ expression has been associated with pulmonary fibrosis in several models of lung injury. Our laboratory as well as other groups have demonstrated the presence of pro-inflammatory cytokines (IL-1, IL-6, IL-8) in the broncho-alveolar lavage fluid from premature neonates (BAL-NN). In the present study, initial measurements by reverse transcripatase polymerase chain reaction demonstrated the presence of TGFβ mRNA in the BAL-derived lung inflammatory cells. We subsequently adapted a novel methodology from the PAI promoter luciferase mink lung epithelial assay (Anal.Biochem.216:276-84,1994) to quantify the levels of active TGFβ protein in BAL-NN. TGFβ bioactivity (TGFβ-BA) was analysed in serial BAL of 16 preterm neonates[6M/10F, mean GA 26 wk (range 23-30), mean BW 774 g (range 555-1075)]. BAL were obtained on day 1 and every 4 days subsequently up to 36 days. We examined the relationship of TGFβ-BA to expression of pro-inflammatory cytokines and inflammatory cell count as the newborns progressed from acute to chronic lung disease. The levels of active TGFβ were initially low in the first 24 hours of life and showed a 3-6 fold increase with TGFβ-BA peaking at day 20-25. The mean TGFβ-BA appears to decrease marginally after the peak but to remain elevated above baseline. On the other hand, pro-inflammatory cytokines and macrophages showed a similar initial pattern but decreased significantly to become almost undetectable at 1 month of life. We have demonstrated that TGFβ is present at an early stage in BAL of preterm neonates and initially follows the pattern of the other cytokines and the macrophages, but remains relatively elevated while the other markers of inflammation decrease. We therefore speculate 1) that TGFβ is involved in the inflammatory and repair process encountered in acute and chronic lung disease of the preterm neonate and 2) that TGFβ probably is produced by several types of cells which vary with the stage of the disease. Supported by the Hastings Foundation.
