Transforming growth factor-beta3 induces pleurodesis in rabbits and collagen production of human mesothelial cells.

Abstract

STUDY OBJECTIVE: The aim of this study was to examined whether transforming growth factor (TGF)-beta(3) induces pleurodesis in rabbits and collagen production by human pleural mesothelial cells in vitro. DESIGN: A combined animal and in vitro study. METHODS: TGF-beta(3) was injected intrapleurally in rabbits at the following doses: 0.167 mug, 0.5 mug, 1.67 mug, and 5 mug (five rabbits per group). The rabbits were killed 14 days following injection, and pleurodesis was graded from 1 (none) to 8 (complete symphysis). Pleural mesothelial cell cultures were established from benign pleural effusions and treated with TGF-beta(3) for 48 h at the following doses: 0 (control), 5 ng/mL, 1.5 ng/mL, 5 ng/mL, and 15 ng/mL and 50 ng/mL (two independent experiments). Collagen I messenger RNA (mRNA) expression was quantified using real-time polymerase chain reaction. RESULTS: The median pleurodesis score was 5 (interquartile range [IQR], 4.5) in the 0.167-mug group, 6 (IQR, 5) in the 0.5-mug group, 8 (IQR, 1) in the 1.67-mug group, and 8 (IQR, 0.5) in the 5-mug group (p = 0.012). Higher TGF-beta(3) doses induced the production of significantly more pleural fluid than the lower doses (p = 0.005). The pleural fluid induced by higher doses contained significantly lower numbers of nucleated cells (p = 0.014) and lactate dehydrogenase levels (p = 0.013) than the pleural fluid induced by lower doses of the agent. TGF-beta(3) markedly enhanced collagen I mRNA expression by the human pleural mesothelial cells. This effect peaked at 5 ng/mL TGF-beta(3). With this dose of TGF-beta(3), the collagen I mRNA expression was increased 16-fold over control levels. CONCLUSION: TGF-beta(3) causes a dose-dependent pleurodesis when administered intrapleurally in rabbits, and induces collagen messenger RNA synthesis from human pleural mesothelial cells.