INTERVENTIONAL PULMONOLOGY IN OTHER JOURNALS: Commentary on Selected Publications
Transforming growth factor and neutralizing antibodies in subglottic stenosis.
Ann Otol Rhinol Laryngol 2001;110:393–400. Dillard DG, Gal AA, Roman–Rodriguez J, White S, Jacobs IN. Department of Otolaryngology, Atlanta Veterans Administration Medical Center and Emory University School of Medicine, Atlanta, Georgia, U.S.A.
This study was designed to test the hypothesis that transforming growth factor beta 1 (TGF-β1) may possibly play a role in the pathogenesis of subglottic stenosis. To study this hypothesis, the authors measured TGF-β1 expression sequentially in 28 adult male Sprague–Dawley rats after posterior cricoid injury, using both standard immunohistochemistry and reverse transcription–polymerase chain reaction. In addition, an osmotic pump infused TGF-β1 in 18 rats, normal saline solution in 9 rats, and neutralizing antibodies in 9 rats. Specimens were stained for fibronectin and procollagen at 1, 7, and 21 days and underwent optical density analysis. The normal controls showed expression of latent TGF-β1 in the respiratory epithelium and submucosal glands. In the injured airway, TGF-β1 expression was most intense during the early periods (1 or 2 days after injury) and returned to the level of uninjured control specimens by day 21. All TGF-β1-infused specimens revealed a marked increase in fibrosis and inflammation relative to the saline infusion control specimens. The TGF-β1 infusion led to a significant increase in the expression of extracellular matrix proteins relative to controls. In contrast, infusion of neutralizing antibodies to TGF-β1 resulted in a decrease in the intensity of fibronectin and type I procollagen staining at the laryngofissure site relative to the saline infusion control and the posterior wound. The authors conclude that the findings from this study suggest that TGF-β1 may possibly play a role in the pathogenesis of subglottic stenosis. This is an elegantly designed study to assess the role of TGF-β1 as a potent mediator of scarring and fibrosis in the injured airways. The idea that TGF-β1, which is implicated in the pathogenesis of fibrotic diseases such as interstitial pulmonary fibrosis, may be associated with subglottic stenosis is attractive, because it follows that administration of neutralizing antibodies to TGF-β1 may have the capacity to thwart progression of scar tissue, whether it is in the lungs or subglottic stenotic lesions. TGF-β1 is a polypeptide growth factor produced by platelets and macrophages. Experimental studies have indicated that TGF-β1 is a potent mediator of scar tissue formation. However, as noted by Dillard et al., TGF-β1 is part of a complex system involved in the formation of scar tissue. Other mechanisms of scar formation have to be understood before a multiprong approach can be applied either to prevent or to treat airway stenosis.