IAN N. JACOBS, MD; DAVID DILLARD, MD; ANTHONY GAL, MD; JESSE ROMAN, MD; STEPHEN WHITE

PHILADELPHIA, PENNSYLVANIA

Transforming growth factor ß-1 (TGF-ß1) 1), which leads to scarring in many organ systems, has never been studied in the larynx. To investigate the role of TGF-ß1 in airway wound healing, we first measured the expression of TGF-ß1 in the injured rat larynx. Twenty-eight rats underwent posterior cricoid de-epithelialization(l x 3-mm area). Cross sections from the midpoint of the injury were stained for activated TGF-ß1 1. The expression of TGF-ß1 1 was compared to that of extracellular matrix (ECM) proteins (fibronectin, tenascin, type III procollagen) in previous studies. To determine the effect of TGF-ß1 on airway wound healing, we implanted an osmotic pump in 12 additional rats to continuously infuse TGF-ß1 directly onto the wound site at 10 ng/h. To decrease scar formation, we infused anti-TGF-ß1 blocking antibodies at 2 ug/h in 12 rats. The staining intensity of all specimens was analyzed by a computerized optical density system. In the injured airway, TGF-ß1 1 expression peaked early (ito 2 days) relative to fibronectin and tenascin, which peaked at 4 days, and type III procollagen, at 7 days. The infusion of TGF-ß1 led to a marked increase in the expression of ECM proteins relative to controls. In contrast, blocking antibodies led to a decrease in ECM protein expression. These data suggest that TGF-ß1 may play a key role in the pathogenesis of subglottic stenosis and that blockade of TGF-ß1 activity may potentially decrease airway scar tissue formation.