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

Area of Science:

• Immunology
• Physiology
• Biochemistry

Background:

• Endothelial indoleamine 2,3-dioxygenase 1 (IDO) excessively metabolizes tryptophan to kynurenine, controlling arterial relaxation and causing hypotension in murine endotoxemia.
• The role of IDO in human endotoxemia remains uninvestigated.

Purpose of the Study:

• To investigate changes in blood pressure alongside tryptophan and kynurenine levels during experimental human endotoxemia.
• To determine the relevance of IDO activity in human endotoxemia and its association with hypotension.

Main Methods:

• Six healthy male volunteers received an intravenous infusion of E. coli lipopolysaccharide (LPS).
• IDO activity was assessed via the kynurenine-to-tryptophan plasma ratio using liquid chromatography-tandem mass spectrometry.
• Levels of soluble E-Selectin and soluble vascular cell adhesion molecule-1 were also measured over a 24-hour period.

Main Results:

• IDO activity significantly increased during endotoxemia, peaking 8 hours post-LPS infusion (44.0 ± 15.2 vs. 29.4 ± 6.8 at baseline, P<0.0001).
• IDO activity showed an inverse correlation with the development of hypotension.
• The kinetic profile of IDO activity mirrored that of soluble endothelial-specific adhesion molecules.

Conclusions:

• Lipopolysaccharide (LPS) triggers IDO induction in humans.
• The findings support the concept that induced IDO in the vascular endothelium contributes to hypotension in human sepsis.