Thromb Haemost 2006; 96(06): 789-793
DOI: 10.1160/TH06-07-0393
Platelets and Blood Cells
Schattauer GmbH

Ethyl pyruvate exerts combined anti-inflammatory and anticoagulant effects on human monocytic cells

Marieke A. D. van Zoelen
1   Center for Infection and Immunity Amsterdam (CINIMA)
2   Center for Experimental and Molecular Medicine
,
Kamran Bakhtiari
3   Departments of Vascular Medicine
,
Mark C. Dessing
1   Center for Infection and Immunity Amsterdam (CINIMA)
2   Center for Experimental and Molecular Medicine
,
Cornelis van ’t Veer
1   Center for Infection and Immunity Amsterdam (CINIMA)
2   Center for Experimental and Molecular Medicine
,
C. Arnold Spek
1   Center for Infection and Immunity Amsterdam (CINIMA)
2   Center for Experimental and Molecular Medicine
,
Michael Tanck
4   Biostatistics; Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Joost C. Meijers
3   Departments of Vascular Medicine
,
Tom van der Poll
1   Center for Infection and Immunity Amsterdam (CINIMA)
2   Center for Experimental and Molecular Medicine
› Author Affiliations

Financial support: This work was supported by Critical Therapeutic Inc., Lexington, Massachussetts, USA.
Further Information

Publication History

Received 13 July 2006

Accepted after resubmission 13 October 2006

Publication Date:
29 November 2017 (online)

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Summary

Sepsis is characterized by a concurrent activation of inflammation and coagulation. Recently, recombinant human activated protein C was shown to decrease mortality in patients with severe sepsis presumably due to a combined anti-inflammatory and anticoagulant effect.These promising findings led to a search for other products that influence both the inflammatory and the procoagulant response to severe infection. Ethyl pyruvate (EP) was recently identified as an experimental anti-inflammatory agent during endotoxemia and sepsis. The aim of the present study was to investigate whether EP influences coagulation besides its anti-inflammatory effects. For this we investigated the effects of EP on the expression and function of tissue factor (TF), the principal initiator of coagulation activation in sepsis, in human monocytic (THP-1) cell cultures. EP dose-dependently inhibited the production of tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1α and MIP-1β by lipopolysaccharide (LPS)-stimulated THP-1 cells at mRNA and protein level, thereby confirming its anti-inflammatory properties in this in-vitro system.In addition, EP dose-dependently attenuated the increases in TF mRNA levels,TF-protein-surface expression and cell-surface-associated TF activity in LPS-stimulated THP-1 cells. These results demonstrate for the first time that EP is a compound with combined anti-inflammatory and anticoagulant effects.