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1 Division of Pulmonary and Critical Care, Vanderbilt University and 2 Pulmonary Dept, St Thomas Hospital, Nashville, TN, USA. 3 Asthma and Allergy Research Institute and University Dept of Medicine, University of Western Australia, Perth, Australia
CORRESPONDENCE: Y.C.G. Lee, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK. Fax: 44 1865287578. E-mail: ycgarylee@hotmail.com
Keywords: fibrosis, interleukin-8, mesothelial, pleura, transforming growth factor-ß
Received: December 2, 2002
Accepted March 12, 2003
This study was supported by the St Thomas Foundation, Nashville, TN, the US Dept of Veterans Affairs and the National Institutes of Health grants HL61419 and HL68121, USA. Y.C.G. Lee is supported by a Wellcome Trust New Zealand Health Research Council TravellingResearch Fellowship and a Graham Aitken Nuffeld Medical Postgraduate Travelling Scholarship, UK.
Abstract
Conventional pleurodesing agents often provoke acute pleural inflammation followed by fibrosis. The inflammation frequently causes pain and fever. Transforming growth factor (TGF)-ß is a pro-fibrotic but anti-inflammatory cytokine. Intrapleural TGF-ß2 administration produces effective pleurodesis in animals, but its effects on mesothelial cells are unknown. The authors hypothesised that, unlike conventional pleurodesing agents, TGF-ß2 can induce collagen synthesis without stimulating pleural inflammation.
In the in vitro studies, TGF-ß2, talc and doxycycline were administered to rabbit mesothelial cells for 24 h. These agents were also injected intrapleurally in rabbits and the induced pleural fluids collected at 24 h. TGF-ß2 was as potent as talc and doxycycline in upregulating mesothelial cell collagen expression.
Talc and doxycycline both induced significant increases in interleukin (IL)-8 production from mesothelial cells in vitro and in rabbit pleural fluids in vivo. TGF-ß2, however, did not stimulate mesothelial cell IL-8 release in vitro and induced a dose-dependent suppression of pleural fluid IL-8. Pleural fluid IL-8 levels correlated significantly with leukocyte and lactate dehydrogenase concentrations in the fluids.
In summary, transforming growth factor-ß was a potent inducer of mesothelial cell collagen synthesis. Unlike talc and tetracycline, which provoked pleural inflammation, transforming growth factor-ß2 suppressed pleural inflammation in vivo. Transforming growth factor-ß2 can produce effective pleural fibrosis without necessitating acute pleural inflammation.
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