Transforming growth factor-beta induces collagen synthesis without inducing IL-8 production in mesothelial cells.
Conventional pleurodesing agents often provoke acute pleural inflammation followed by fibrosis. The inflammation frequently causes pain and fever. Transforming growth factor (TGF)-beta is a pro-fibrotic but anti-inflammatory cytokine. Intrapleural TGF-beta2 administration produces effective pleurodesis in animals, but its effects on mesothelial cells are unknown. The authors hypothesised that, unlike conventional pleurodesing agents, TGF-beta2 can induce collagen synthesis without stimulating pleural inflammation. In the in vitro studies, TGF-beta2, 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-beta2 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-beta2, 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-beta was a potent inducer of mesothelial cell collagen synthesis. Unlike talc and tetracycline, which provoked pleural inflammation, transforming growth factor-beta2 suppressed pleural inflammation in vivo. Transforming growth factor-beta2 can produce effective pleural fibrosis without necessitating acute pleural inflammation.
Lee
Y C G
YC
Division of Pulmonary and Critical Care, Vanderbilt University, Nashville, TN, USA. ycgarylee@hotmail.com
Lane
K B
KB
Zoia
O
O
Thompson
P J
PJ
Light
R W
RW
Blackwell
T S
TS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000008:administration & dosage; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D007267:Injections; D016209:Interleukin-8 / Q000096:biosynthesis*; D010994:Pleura / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D013627:Talc / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
D000900:Anti-Bacterial Agents; D016209:Interleukin-8; D016212:Transforming Growth Factor beta; D013627:Talc; D003094:Collagen; D004318:Doxycycline