Transforming growth factor β2 (TGFβ2) produces effective pleurodesis in sheep with no systemic complications

Abstract

Background - We have recently shown that transforming growth factor (TGF)β2 induces effective pleurodesis in rabbits. However, rabbits have a thin pleura while humans have a thick visceral pleura. The effect of intrapleural administration of TGFβ2 in animals with a thick pleura and its associated systemic effects have not been investigated. This study was undertaken (1) to develop a new animal model for the study of pleurodesis using sheep which have a thick pleura resembling that of humans; (2) to study the efficacy of TGFβ2 as a pleurodesis agent in the sheep model; and (3) to assess whether histological changes occur in extrapulmonary organs after intrapleural administration of TGFβ2. Methods - Twelve sheep were divided into four groups and were given a single intrapleural injection of TGFβ2 in a concentration of 1.0 μg/kg, 0.5 μg/kg, 0.25 μg/kg or 0.125 μg/kg to the right pleural cavity via a chest tube. The left pleural cavity served as the control. Any pleural fluid that accumulated after the intrapleural TGFβ2 injection was collected and analysed. The degree of pleurodesis was graded from 1 (no adhesions) to 8 (complete symphysis >50% of chest wall) at day 14 when the sheep were killed. Biopsy specimens were taken from the lungs and extrapulmonary organs. Results - All sheep that received ≥0.25 μg/kg TGFβ2 developed excellent pleurodesis (score = 8) while those that received 0.125 μg/kg had a median score of 6. The pleurodesis score did not exceed 2 in the control (left) side of any sheep. Sheep receiving ≥0.50 μg/kg TGFβ2 developed large exudative pleural effusions while those receiving a lower dose did not. The production of effusions neither hindered nor was necessary for inducing pleurodesis. There were no significant fibrotic changes in any of the extrapulmonary organs. Conclusion - Intrapleural injection of 0.25-1.0 μg/kg TGFβ2 produces excellent pleurodesis in a new sheep model with no evidence of extrapulmonary fibrosis.