Inability of lipid A murine specific monoclonal antibody E5 to neutralize lipopolysaccharide biological activity in vitro

AS Bouter; KPM van Kessel; JJ Cornelissen; JFP Schellekens; H. Snippe; J. Verhoef

doi:10.1016/0888-0786(94)90007-8

Inability of lipid A murine specific monoclonal antibody E5 to neutralize lipopolysaccharide biological activity in vitro

AS Bouter^*, KPM van Kessel, JJ Cornelissen, JFP Schellekens, H. Snippe, J. Verhoef

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

4 Citations (Scopus)

Abstract

The use of anti-endotoxin monoclonal antibodies (mAbs) for the therapy of Gramnegative sepsis is controversial. Murine mAb E5, reactive with different rough and smooth lipopolysaccharides (LPS) and lipid A, has been evaluated in several experimental models and clinical trials. In the present study mAb E5 was evaluated for its capacity to neutralize toxic effects of LPS in vitro to understand the biologic basis for its proposed activity in vivo. Despite the use of high concentrations of mAb, E5 did not significantly neutralize LPS as assessed by LPS induced priming of neutrophil oxidative burst, adhesion of granulocytes to LPS stimulated endothelial cells or the release of cytokines (tumour necrosis factor (TNF) and interleukin (IL1β and IL6) from monocytes in an ex vivo whole blood stimulation assay. It was concluded that the proposed protective capacity of mAb E5 in vivo can not be explained by neutralization of the investigated endotoxin effects in vitro.

Original language	English
Pages (from-to)	35-39
Number of pages	5
Journal	Serodiagnosis and Immunotherapy in Infectious Disease
Volume	6
Issue number	1
DOIs	https://doi.org/10.1016/0888-0786(94)90007-8
Publication status	Published - 1 Jan 1994

Keywords

cytokines
endothelium
Endotoxin
leukocytes

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title = "Inability of lipid A murine specific monoclonal antibody E5 to neutralize lipopolysaccharide biological activity in vitro",

abstract = "The use of anti-endotoxin monoclonal antibodies (mAbs) for the therapy of Gramnegative sepsis is controversial. Murine mAb E5, reactive with different rough and smooth lipopolysaccharides (LPS) and lipid A, has been evaluated in several experimental models and clinical trials. In the present study mAb E5 was evaluated for its capacity to neutralize toxic effects of LPS in vitro to understand the biologic basis for its proposed activity in vivo. Despite the use of high concentrations of mAb, E5 did not significantly neutralize LPS as assessed by LPS induced priming of neutrophil oxidative burst, adhesion of granulocytes to LPS stimulated endothelial cells or the release of cytokines (tumour necrosis factor (TNF) and interleukin (IL1β and IL6) from monocytes in an ex vivo whole blood stimulation assay. It was concluded that the proposed protective capacity of mAb E5 in vivo can not be explained by neutralization of the investigated endotoxin effects in vitro.",

keywords = "cytokines, endothelium, Endotoxin, leukocytes",

author = "AS Bouter and {van Kessel}, KPM and JJ Cornelissen and JFP Schellekens and H. Snippe and J. Verhoef",

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AU - Bouter, AS

AU - van Kessel, KPM

AU - Cornelissen, JJ

AU - Schellekens, JFP

AU - Snippe, H.

AU - Verhoef, J.

PY - 1994/1/1

Y1 - 1994/1/1

N2 - The use of anti-endotoxin monoclonal antibodies (mAbs) for the therapy of Gramnegative sepsis is controversial. Murine mAb E5, reactive with different rough and smooth lipopolysaccharides (LPS) and lipid A, has been evaluated in several experimental models and clinical trials. In the present study mAb E5 was evaluated for its capacity to neutralize toxic effects of LPS in vitro to understand the biologic basis for its proposed activity in vivo. Despite the use of high concentrations of mAb, E5 did not significantly neutralize LPS as assessed by LPS induced priming of neutrophil oxidative burst, adhesion of granulocytes to LPS stimulated endothelial cells or the release of cytokines (tumour necrosis factor (TNF) and interleukin (IL1β and IL6) from monocytes in an ex vivo whole blood stimulation assay. It was concluded that the proposed protective capacity of mAb E5 in vivo can not be explained by neutralization of the investigated endotoxin effects in vitro.

AB - The use of anti-endotoxin monoclonal antibodies (mAbs) for the therapy of Gramnegative sepsis is controversial. Murine mAb E5, reactive with different rough and smooth lipopolysaccharides (LPS) and lipid A, has been evaluated in several experimental models and clinical trials. In the present study mAb E5 was evaluated for its capacity to neutralize toxic effects of LPS in vitro to understand the biologic basis for its proposed activity in vivo. Despite the use of high concentrations of mAb, E5 did not significantly neutralize LPS as assessed by LPS induced priming of neutrophil oxidative burst, adhesion of granulocytes to LPS stimulated endothelial cells or the release of cytokines (tumour necrosis factor (TNF) and interleukin (IL1β and IL6) from monocytes in an ex vivo whole blood stimulation assay. It was concluded that the proposed protective capacity of mAb E5 in vivo can not be explained by neutralization of the investigated endotoxin effects in vitro.

KW - cytokines

KW - endothelium

KW - Endotoxin

KW - leukocytes

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Inability of lipid A murine specific monoclonal antibody E5 to neutralize lipopolysaccharide biological activity in vitro

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