The acute respiratory distress syndrome -: A role for transforming growth factor-β1

The acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality. Enhanced fibrosis and elevated procollagen III levels have been linked to increased mortality. We hypothesized that transforming growth factor (TGF)-beta1 may play an important role in ARDS, given its role in stimulating fibrosis. Using reverse transcriptase in situ polymerase chain reaction (RT in situ PCR) and immunohistochemistry, we analyzed lung tissue from four fibroproliferative ARDS cases and control subjects. We also compared active TGF-beta1 levels in the bronchoalveolar lavage (BAL) fluid of 13 de novo ARDS cases, and 7 normal control subjects. RT in situ PCR showed TGF-beta1 mRNA expression in fibroproliferative ARDS cases. Immunohistochemistry confirmed protein expression in these samples. Controls were negative for both techniques. In the newly enrolled ARDS cases, TGF-beta1 levels, as measured by luciferase assay, were elevated in the 11 of 13 samples, averaging 98 +/- 40 pg/mg protein. Controls had no detectable TGF-beta1 activity. These data suggest that activation of TGF-beta1 may be important in the early phases of acute lung injury in addition to driving fibroproliferation. These data may lead to new therapeutic approaches in ARDS through more targeted inhibition of fibrosis.