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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article numberR97
JournalCritical Care
Volume17
Issue number3
DOIs
Publication statusPublished - 2013 May 27

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Vascular Endothelial Growth Factor A
Sepsis
Theoretical Models
Punctures
Endotoxemia
Inflammation
Ligation
Human Umbilical Vein Endothelial Cells
Lipopolysaccharides
Mortality
Antibodies
Cytokines
Survival
Reverse Transcription
Blood Vessels
Permeability
Therapeutics
Spleen
Kidney
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Cite this

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title = "Anti-vascular endothelial growth factor antibody attenuates inflammation and decreases mortality in an experimental model of severe sepsis",
abstract = "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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Anti-vascular endothelial growth factor antibody attenuates inflammation and decreases mortality in an experimental model of severe sepsis. / Jeong, Su Jin; Han, Sang Hoon; Kim, Chang Oh; Choi, Jun Yong; Kim, June Myung.

In: Critical Care, Vol. 17, No. 3, R97, 27.05.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anti-vascular endothelial growth factor antibody attenuates inflammation and decreases mortality in an experimental model of severe sepsis

AU - Jeong, Su Jin

AU - Han, Sang Hoon

AU - Kim, Chang Oh

AU - Choi, Jun Yong

AU - Kim, June Myung

PY - 2013/5/27

Y1 - 2013/5/27

N2 - 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.

AB - 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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DO - 10.1186/cc12742

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