title: Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia.
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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus A1, Münster 48149, Germany.
authors.forename: Jan-Sören
authors.initials: JS
authors.lastname: Padberg
authors.affiliation: Department of Critical Care, University Medical Center Groningen, Hanzeplein 1, University of Groningen, Groningen, GZ, 9713, The Netherlands.|Department of Pathology and Medical Biology, University Medical Center Groningen, Hanzeplein 1, University of Groningen, Groningen, GZ, 9713, The Netherlands.
authors.forename: Matijs
authors.initials: M
authors.lastname: Van Meurs
authors.affiliation: Department of Nephrology & Hypertension, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany.
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kielstein
authors.affiliation: Institute for Clinical Pharmacology, Otto-von-Guericke University Magdeburg, Leipziger Straße 44, Magdeburg, 39120, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Martens-Lobenhoffer
authors.affiliation: Institute for Clinical Pharmacology, Otto-von-Guericke University Magdeburg, Leipziger Straße 44, Magdeburg, 39120, Germany.
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Bode-Böger
authors.affiliation: Department of Critical Care, University Medical Center Groningen, Hanzeplein 1, University of Groningen, Groningen, GZ, 9713, The Netherlands.
authors.forename: Jan G
authors.initials: JG
authors.lastname: Zijlstra
authors.affiliation: Divisions of Nephrology, University of Virginia, Charlottesville, Virginia & Salem VA Medical Center 1970 Roanoke Blvd, Salem, VA, 24153, USA.
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus A1, Münster 48149, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kümpers