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Laboratory and Animal Investigations |

Transforming Growth Factor-β3 Induces Pleurodesis in Rabbits and Collagen Production of Human Mesothelial Cells*

Ioannis Kalomenidis, MD; Yubiao Guo, MD; Kirk B. Lane, PhD; Michael Hawthorne, MD; Richard W. Light, MD, FCCP
Author and Funding Information

*From the Department of Critical Care and Pulmonary Services (Dr. Kalomenidis), Athens Medical School, Evangelismos Hospital, Athens, Greece; the Department of Allergy Pulmonary and Critical Care Medicine (Dr. Light), Vanderbilt University, Nashville, TN; the Department of Pulmonary Medicine (Drs. Lane and Hawthorne), St. Thomas Hospital and Vanderbilt University, Nashville, TN; and Department of Respiratory & Critical Care Medicine (Dr. Guo), First Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.

Correspondence to: Ioannis Kalomenidis, MD, Department of Critical Care and Pulmonary Services, Athens Medical School, Evangelismos Hospital, 45–47 Ipsilantou, 10675, Athens, Greece; e-mail: jkalomenidis@hotmail.com



Chest. 2005;127(4):1335-1340. doi:10.1378/chest.127.4.1335
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Study objective: The aim of this study was to examined whether transforming growth factor (TGF)-β3 induces pleurodesis in rabbits and collagen production by human pleural mesothelial cells in vitro.

Design: A combined animal and in vitro study.

Methods: TGF-β3 was injected intrapleurally in rabbits at the following doses: 0.167 μg, 0.5 μg, 1.67 μg, and 5 μg (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-β3 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-μg group, 6 (IQR, 5) in the 0.5-μg group, 8 (IQR, 1) in the 1.67-μg group, and 8 (IQR, 0.5) in the 5-μg group (p = 0.012). Higher TGF-β3 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-β3 markedly enhanced collagen I mRNA expression by the human pleural mesothelial cells. This effect peaked at 5 ng/mL TGF-β3. With this dose of TGF-β3, the collagen I mRNA expression was increased 16-fold over control levels.

Conclusion: TGF-β3 causes a dose-dependent pleurodesis when administered intrapleurally in rabbits, and induces collagen messenger RNA synthesis from human pleural mesothelial cells.

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