title: Soluble vascular endothelial growth factor receptor-1 protects mice in sepsis.
abstract: OBJECTIVE
  To determine the putative role in the modulation of inflammation of a soluble form of Flt-1 (sFlt), a potent vascular endothelial growth factor antagonist, in experimental endotoxemia and sepsis.
  
  
  METHODS
  Randomized prospective experimental study.
  
  
  METHODS
  University medical laboratory.
  
  
  METHODS
  Male C56BL/6 strain mice.
  
  
  METHODS
  We investigated the expression patterns and the effects of vascular endothelial growth factor and soluble Flt-1 in experimental endotoxic shock and sepsis. The possible anti-inflammatory mechanism of soluble Flt-1 was also evaluated.
  
  
  RESULTS
  Both vascular endothelial growth factor and sFlt-1 were rapidly released from macrophages activated in vitro by lipopolysaccharide and in the plasma of endotoxemic mice. Administration of vascular endothelial growth factor enhanced proinflammatory cytokine production and mediated a dramatic increase in mortality in endotoxemic mice. Treatment with sFlt-1 attenuated inflammatory responses, inhibited recruitment of inflammatory cells into the peritoneal cavity, and improved survival in a lethal endotoxemia and cecal ligation and puncture-induced sepsis model, even when administered as late as 24 hrs after the onset of sepsis.
  
  
  CONCLUSIONS
  These findings support a critical protective role of sFlt-1 in endotoxic shock and sepsis. sFlt-1 may therefore have utility as an adjunctive agent for the treatment of sepsis syndrome.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. tsaopn@ntu.edu.tw
authors.forename: Po-Nien
authors.initials: PN
authors.lastname: Tsao
authors.forename: Feng-Tsan
authors.initials: FT
authors.lastname: Chan
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Wei
authors.forename: Wu-Shiun
authors.initials: WS
authors.lastname: Hsieh
authors.forename: Hung-Chieh
authors.initials: HC
authors.lastname: Chou
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.forename: Chien-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Hsu
authors.forename: Fon-Jou
authors.initials: FJ
authors.lastname: Hsieh
authors.forename: Su-Ming
authors.initials: SM
authors.lastname: Hsu
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000187:drug effects; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000627:therapeutic use*
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1