Soluble vascular endothelial growth factor receptor-1 protects mice in sepsis.
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.
Tsao
Po-Nien
PN
Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. tsaopn@ntu.edu.tw
Chan
Feng-Tsan
FT
Wei
Shu-Chen
SC
Hsieh
Wu-Shiun
WS
Chou
Hung-Chieh
HC
Su
Yi-Ning
YN
Chen
Chien-Yi
CY
Hsu
Wen-Ming
WM
Hsieh
Fon-Jou
FJ
Hsu
Su-Ming
SM
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*
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