title: Monoclonal anti-vascular endothelial growth factor antibody reduces fluid volume in an experimental model of inflammatory pleural effusion.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) is known to increase vascular permeability and promote angiogenesis. It is expressed in most types of pleural effusions. However, the exact role of VEGF in the development of pleural effusions has yet to be determined. The anti-VEGF mAb, bevacizumab, has been used in the treatment of cancer to reduce local angiogenesis and tumour progression. This study describes the acute effects of VEGF blockade on the expression of inflammatory cytokines and pleural fluid accumulation.
  
  
  METHODS
  One hundred and twelve New Zealand rabbits received intrapleural injections of either talc or silver nitrate. In each group, half the animals received an intravenous injection of bevacizumab, 30 min before the intrapleural agent was administered. Five animals from each subgroup were sacrificed 1, 2, 3, 4 or 7 days after the procedure. Twelve rabbits were used to evaluate vascular permeability using Evans's blue dye. Pleural fluid volume and cytokines were quantified.
  
  
  RESULTS
  Animals pretreated with anti-VEGF antibody showed significant reductions in pleural fluid volumes after talc or silver nitrate injection. IL-8 levels, vascular permeability and macroscopic pleural adhesion scores were also reduced in the groups that received bevacizumab.
  
  
  CONCLUSIONS
  This study showed that bevacizumab interferes in the acute phase of pleural inflammation induced by silver nitrate or talc, reinforcing the role of VEGF as a key mediator in the production of pleural effusions. The results also suggest that bevacizumab should probably be avoided in patients requiring pleurodesis.
authors.affiliation: Laboratory of Pleura, Pulmonary Division, Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil. sabrinaccr@gmail.com
authors.forename: Sabrina C C
authors.initials: SC
authors.lastname: Ribeiro
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Vargas
authors.forename: Leila
authors.initials: L
authors.lastname: Antonangelo
authors.forename: Evaldo
authors.initials: E
authors.lastname: Marchi
authors.forename: Eduardo H
authors.initials: EH
authors.lastname: Genofre
authors.forename: Milena M P
authors.initials: MM
authors.lastname: Acencio
authors.forename: Lisete R
authors.initials: LR
authors.lastname: Teixeira
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002199:Capillary Permeability / Q000502:physiology; D000075202:Contraindications; D004195:Disease Models, Animal; D016209:Interleukin-8 / Q000378:metabolism; D010996:Pleural Effusion / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D018700:Pleurodesis; D011817:Rabbits; D012835:Silver Nitrate / Q000009:adverse effects; D013627:Talc / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; D013627:Talc; D000068258:Bevacizumab; D012835:Silver Nitrate