Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia

Jan Sören Padberg, Matijs Van Meurs, Jan T. Kielstein, Jens Martens-Lobenhoffer, Stefanie M. Bode-Böger, Jan G. Zijlstra, Csaba Kovesdy, Philipp Kümpers

Research output: Contribution to journalArticle

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Abstract

Background: Excessive tryptophan metabolism to kynurenine by the rate-limiting enzyme endothelial indoleamine 2,3-dioxygenase 1 (IDO) controls arterial vessel relaxation and causes hypotension in murine endotoxemia. However, its relevance in human endotoxemia has not been investigated so far. We thus aimed to study changes in blood pressure in parallel with tryptophan and kynurenine levels during experimental endotoxemia in humans.Findings: Six healthy male volunteers were given E. coli lipopolysaccharide (LPS; 4 ng/kg) as a 1-min intravenous infusion. They had levels of soluble E-Selectin and soluble vascular cell adhesion molecule-1 as well as IDO activity assessed as the kynurenine-to-tryptophan plasma ratio by liquid chromatography-tandem mass spectrometry at various time points during a 24 h time course. During endotoxemia, IDO activity significantly increased, reaching peak levels at 8 h after LPS infusion (44.0 ± 15.2 vs. 29.4 ± 6.8 at baseline, P<0.0001). IDO activity correlated inversely with the development of hypotension as shown by random effects linear regression models. Finally, IDO activity exhibited a kinetic profile similar to that of soluble endothelial-specific adhesion molecules.Conclusions: LPS is a triggering factor for the induction of IDO in men. Our findings strongly support the concept that the induction of IDO in the vascular endothelium contributes to hypotension in human sepsis.

Original languageEnglish (US)
Article number24
JournalExperimental and Translational Stroke Medicine
Volume4
Issue number1
DOIs
StatePublished - Dec 5 2012

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Endotoxemia
Kynurenine
Tryptophan
Hypotension
Linear Models
E-Selectin
Vascular Cell Adhesion Molecule-1
Vascular Endothelium
Tandem Mass Spectrometry
Intravenous Infusions
Liquid Chromatography
Lipopolysaccharides
Sepsis
Healthy Volunteers
Escherichia coli
Blood Pressure
Enzymes

All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Cognitive Neuroscience

Cite this

Padberg, J. S., Van Meurs, M., Kielstein, J. T., Martens-Lobenhoffer, J., Bode-Böger, S. M., Zijlstra, J. G., ... Kümpers, P. (2012). Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia. Experimental and Translational Stroke Medicine, 4(1), [24]. https://doi.org/10.1186/2040-7378-4-24

Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia. / Padberg, Jan Sören; Van Meurs, Matijs; Kielstein, Jan T.; Martens-Lobenhoffer, Jens; Bode-Böger, Stefanie M.; Zijlstra, Jan G.; Kovesdy, Csaba; Kümpers, Philipp.

In: Experimental and Translational Stroke Medicine, Vol. 4, No. 1, 24, 05.12.2012.

Research output: Contribution to journalArticle

Padberg, JS, Van Meurs, M, Kielstein, JT, Martens-Lobenhoffer, J, Bode-Böger, SM, Zijlstra, JG, Kovesdy, C & Kümpers, P 2012, 'Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia', Experimental and Translational Stroke Medicine, vol. 4, no. 1, 24. https://doi.org/10.1186/2040-7378-4-24
Padberg JS, Van Meurs M, Kielstein JT, Martens-Lobenhoffer J, Bode-Böger SM, Zijlstra JG et al. Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia. Experimental and Translational Stroke Medicine. 2012 Dec 5;4(1). 24. https://doi.org/10.1186/2040-7378-4-24
Padberg, Jan Sören ; Van Meurs, Matijs ; Kielstein, Jan T. ; Martens-Lobenhoffer, Jens ; Bode-Böger, Stefanie M. ; Zijlstra, Jan G. ; Kovesdy, Csaba ; Kümpers, Philipp. / Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia. In: Experimental and Translational Stroke Medicine. 2012 ; Vol. 4, No. 1.
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