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Anti-vascular endothelial growth factor antibody attenuates inflammation and decreases mortality in an experimental model of severe sepsis

 Su Jin Jeong  ;  Sang Hoon Han  ;  Chang Oh Kim  ;  Jun Yong Choi  ;  June Myung Kim 
 CRITICAL CARE, Vol.17(3) : 97, 2013 
Journal Title
Issue Date
Animals ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Bevacizumab ; Disease Models, Animal* ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Inflammation/drug therapy ; Inflammation/metabolism ; Inflammation/mortality ; Lipopolysaccharides/toxicity ; Mice ; Mice, Inbred C57BL ; Sepsis/drug therapy* ; Sepsis/metabolism ; Sepsis/mortality* ; Vascular Endothelial Growth Factor A/antagonists & inhibitors* ; Vascular Endothelial Growth Factor A/metabolism
sepsis ; vascular endothelial growth factor ; bevacizumab ; anti-VEGF antibody
INTRODUCTION: Severe sepsis is associated with an unacceptably high rate of mortality. Recent studies revealed elevated levels of vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, in patients with sepsis. There was also an association between VEGF levels and sepsis severity. Here we investigate the effects of an anti-VEGF antibody (Bevacizumab, Bev) in an experimental model of sepsis.
METHODS: Human umbilical vein endothelial cells (HUVECs), murine cecal ligation and puncture (CLP), and endotoxemia models of sepsis were used. HUVECs were treated with lipopolysaccharide (LPS) and/or Bev, harvested and cytokine mRNA levels determined using a semi-quantitative reverse transcription-polymerase chain reaction assay. The levels of inflammatory cytokine were also determined in HUVECs supernatants. In addition, the effects of Bev on mortality in the CLP and endotoxemia models of sepsis were evaluated.
RESULTS: Treatment with Bev and LPS significantly decreased the expression and the level of inflammatory cytokines in HUVECs relative to LPS alone. In CLP and endotoxemia models, survival benefits were evident in mice given 0.1 mg/kg of Bev relative to the CLP or LPS alone (P <0.001 and P = 0.028, respectively), and in 6 h post-treated mice relative to the CLP alone for the effect of different time of Bev (P = 0.033). In addition, Bev treatment inhibited LPS-induced vascular leak in the lung, spleen and kidney in the murine endotoxemia model (P <0.05).
CONCLUSIONS: Anti-VEGF antibody may be a promising therapeutic agent due to its beneficial effects on the survival of sepsis by decreasing inflammatory responses and endothelial permeability.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, June Myung(김준명)
Kim, Chang Oh(김창오) ORCID logo https://orcid.org/0000-0002-0773-5443
Jeong, Su Jin(정수진) ORCID logo https://orcid.org/0000-0003-4025-4542
Choi, Jun Yong(최준용) ORCID logo https://orcid.org/0000-0002-2775-3315
Han, Sang Hoon(한상훈) ORCID logo https://orcid.org/0000-0002-4278-5198
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