Am. J. Respir. Crit. Care Med., Volume 162, Number 1, July 2000, 98-104

A Single Intrapleural Injection of Transforming Growth Factor-₂ Produces an Excellent Pleurodesis in Rabbits

RICHARD W. LIGHT, DONG-SHENG CHENG, Y. C.(GARY)  LEE, JEFFREY ROGERS, JEFFREY DAVIDSON, and KIRK B. LANE

Department of Medicine, Saint Thomas Hospital, and Center for Lung Research and Pathology, Vanderbilt University, Nashville, Tennessee

The purpose of the present study was to determine whether the intrapleural injection of transforming growth factor ₂ (TGF-₂) would produce a pleurodesis in rabbits. Single intrapleural injections of TGF-₂ at doses of 5.00 µg (n = 12), 1.67 µg (n = 10), 0.50 µg (n = 10), or 0.167 µg (n = 4), or of the parenteral buffer alone (n = 5) were given in a volume of 2 ml to New Zealand white rabbits. Chest tubes were left in place for at least 72 h. Pleural fluid was aspirated at 24-h intervals and was measured and subjected to chemical analysis. The animals were killed 14 d after the injection. The intrapleural injection of TGF-₂ resulted in a dose-dependent pleurodesis (on a scale of 0 to 4, where 0 = no pleurodesis and 4 = complete pleurodesis) with mean scores of 3.6, 2.6, 1.5, 0.7, and 0.3 for the groups that received 5.0, 1.67, 0.50, and 0.167 µg of TGF-₂ and buffer alone, respectively. Intrapleural injection of the larger doses of TGF-₂ resulted in the formation of a large amount of pleural fluid. The fluid had a significantly lower white blood cell (WBC) count and lactate dehydrogenase (LDH) level than did the fluid that results from the intrapleural injection of 10 mg/kg doxycycline or 400 mg/kg talc slurry. On the basis of this study we conclude that a single intrapleural injection of TGF-₂ induces pleurodesis in a dose-dependent manner. A dose of 5.0 µg produced satisfactory pleurodesis in almost all of the rabbits so treated. Larger doses of TGF-₂ induced larger pleural effusions with relatively low pleural fluid WBC counts and LDH levels. The ability of TGF- to produce a pleurodesis in patients with recurrent pleural effusions or pneumothorax should be investigated. A single intrapleural injection of TGF-₂ may produce a pleurodesis both safely and painlessly.

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