title: [Effect of anti-vascular endothelial growth factor antibody on pleurodesis induced by transforming growth factor-beta or doxycycline in rabbits].
abstract: OBJECTIVE
  The intrapleural injection of transforming growth factor-beta (TGF-beta) or doxycycline produces excellent pleurodesis in rabbit models. However, the intrapleural injection of these agents induces large pleural effusion which is possibly related to vascular endothelial growth factor (VEGF). This study investigated whether anti-VEGF antibody has any effect on the fluid production or the pleurodesis induced by TGF-beta or doxycycline in rabbits.
  
  
  METHODS
  Two groups of New Zealand white rabbits (7 each) were given TGF-beta 5.0 microg intrapleurally. The TGF-beta treatment group received anti-VEGF antibody 10 mg/kg intravenously 24 h before TGF-beta injection and the TGF-beta control group received no antibody. Another two groups of New Zealand white rabbits (7 each) were given doxycycline 10 mg/kg intrapleurally after chest tube placement. The doxycycline treatment group received 10 mg/kg anti-VEGF antibody intravenously 24 h before doxycycline injection and the doxycycline control group received no Anti-VEGF antibody. The rabbits were sacrificed at 2 weeks and the pleurodesis score was graded macroscopically on a 1-8 scale. The degree of angiogenesis in pleural tissues was assessed by immunohistochemical staining for factor VIII which was assessed by computer-assisted digital analysis.
  
  
  RESULTS
  The administration of anti-VEGF antibodies had no effect on pleural fluid volume or the characteristics of the fluid. The mean pleurodesis score of TGF-beta control group (7.7 +/- 0.8) was significantly (P < 0.05) higher than that of the antibody pre-treatment TGF-beta group (4.4 +/- 2.4). The mean pleurodesis score of the doxycycline control group (6.0 +/- 1.7) was significantly (P < 0.05) higher than that of the antibody pre-treatment doxycycline group (2.0 +/- 0.9). The administration of the anti-VEGF antibody also reduced the angiogenesis. The percentage of pleural tissue demonstrating angiogenesis in the TGF-beta control group (4.9 +/- 0.4)% was significantly (P < 0.05) higher than that of the antibody treatment TGF-beta group (2.9 +/- 0.7)%. The percentage of pleural angiogenesis in the doxycycline control group (6.9 +/- 2.2)% was significantly (P < 0.05) higher than the antibody pre-treatment doxycycline group (2.2 +/- 0.9)%.
  
  
  CONCLUSIONS
  Anti-VEGF antibody significantly inhibits the pleurodesis induced by doxycycline or TGF-beta. This observation suggests that VEGF and angiogenesis play a pivotal role in the production of pleurodesis.
authors.affiliation: Department of Respiratory Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Yu-biao
authors.initials: YB
authors.lastname: Guo
authors.forename: Can-mao
authors.initials: CM
authors.lastname: Xie
authors.forename: Richard W
authors.initials: RW
authors.lastname: Light
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D004318:Doxycycline / Q000009:adverse effects; D008297:Male; D010994:Pleura / Q000187:drug effects / Q000473:pathology; D010995:Pleural Diseases / Q000139:chemically induced / Q000276:immunology*; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
chemical_list: D000906:Antibodies; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D004318:Doxycycline