Am. J. Respir. Crit. Care Med., Volume 163, Number 3, March 2001, 640-644

Transforming Growth Factor-₂ Induces Pleurodesis Significantly Faster than Talc

Y. C. GARY LEE, LISETE R. TEIXEIRA, CLINTON J. DEVIN, MARCELO A. C. VAZ, FRANCISCO S. VARGAS, PHILIP J. THOMPSON, KIRK B. LANE, and RICHARD W. LIGHT

Departments of Pulmonary Medicine, St. Thomas Hospital and Vanderbilt University, Nashville, Tennessee; Division of Respiratory Diseases-Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil; and Department of Medicine, University of Western Australia, Perth, Australia

Transforming growth factor-₂ (TGF-₂) has recently been shown to produce effective pleurodesis in rabbits. Conventional pleurodesing agents such as talc act by inducing pleural injury, which results in acute inflammation and fibrosis. TGF-₂ is a profibrotic cytokine capable of producing fibrosis without inducing significant pleural inflammation. We hypothesize that intrapleural administration of TGF-₂ would (1) produce an effective pleurodesis faster; (2) stimulate more collagen deposition, and (3) induce less inflammation when compared with intrapleural injection of talc. Thirty rabbits were divided into two groups and given either TGF-₂ (1.7 µg) or talc slurry (400 mg/kg) via a chest tube. Five rabbits from each group were killed at Days 1, 4, and 7. Gross pleurodesis was graded from 1 (none) to 8 (complete symphysis). The microscopic pleural inflammation and fibrosis were graded from 0 to 4. Pleural thickening and the total area of collagen deposition were compared. Intrapleural injection of TGF-₂ produced effective pleurodesis within 7 d (median pleurodesis score = 7 at Day 7). At Day 7, TGF-₂ induced significantly more collagen deposition (19.4 ± 19.6% versus 4.6 ± 2.9% of total area of pleura at Day 7), higher pleural fibrosis score (3.0 ± 1.0 versus 1.8 ± 0.5), and pleural thickness (286 ± 191 versus 85 ± 37 µm) than did talc. There was no difference in the degree of pleural inflammation between the two groups at Day 7 (2.6 ± 0.9 for TGF-₂ versus 2.4 ± 0.6 for talc) or at any other time points. In conclusion, the intrapleural administration of TGF-₂ produced excellent pleurodesis in rabbits at a rate faster than talc slurry and all other pleurodesing agents investigated before. TGF-₂ stimulated more collagen deposition without inducing excess inflammation when compared with talc slurry. TGF-₂ may have advantages over talc slurry in the management of recurrent pleural effusion and pneumothorax.

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