Transforming growth factor-β: A mediator of cell regulation in acute respiratory distress syndrome

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Abstract
To review recent advances in the use of transforming growth factor (TGF)-β in acute lung injury and to apply this knowledge to understanding the pathophysiology of this syndrome. Published research and review articles in the English language related to the role of TGF-β in acute lung injury. The cytokine TGF-β plays a critical role in the resolution of tissue injury in multiple organs, including the lung. Following injury, TGF-β has been most thoroughly evaluated during the late phases of tissue repair, where it plays a critical role in the development of pulmonary fibrosis. In contrast, recent animal studies showed that expression levels of several TGF-β-inducible genes were dramatically increased as early as 2 days after the induction of injury. The integrin αvβ6 activates latent TGF-β in the lungs. Mice lacking this integrin were completely protected from pulmonary edema in a model of bleomycin-induced acute lung injury. Pharmacologic inhibition of TGF-β also protected wild-type mice from pulmonary edema induced by bleomycin or Escherichia coli endotoxin. Similar findings also have been reported in patients in a clinical study evaluating TGF-β in the bronchoalveolar lavage fluid during the course of acute respiratory distress syndrome (ARDS). Indeed, the bronchoalveolar lavage concentrations were dramatically increased as early as 1 day after the initiation of ARDS criteria and were correlated with decreases in the Pao2/Fio2 ratio, suggesting an important role for TGF-b1 in the development of ARDS in humans. These studies suggest that TGF-β not only participates in the late phase of acute lung injury, but also might be active early in acute lung injury and potentially could contribute to the development of pulmonary edema. Integrin-mediated local activation of TGF-β is critical to the development of pulmonary edema in ARDS, and blocking TGF-β or its activation could be an effective treatment for this disorder.

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