Abstract 3679: Kynurenine is a Novel Vasodilator in Human Septic Shock

Kynurenine is produced when the enzyme indoleamine 2,3-dioxygenase (IDO) metabolises the essential amino acid tryptophan. IDO expression is induced in endothelial cells of resistance vessels when mice are infected with malaria (a model of systemic inflammation). These mice become hypotensive and treatment with 1-methyl-tryptophan, an IDO inhibitor, restores normal blood pressure. In vitro vessel function studies have shown that kynurenine acts as an endothelium-independent relaxant. Kynurenine contributes to the hypotension in human septic shock. Patients admitted to ICU with a diagnosis of septic shock (sepsis with hypotension not responsive to fluids) had serum levels of kynurenine and tryptophan measured throughout the course of their illness. Systemic IDO activity was inferred from the kynurenine/tryptophan ratio and was correlated with the degree of hypotension assessed as each patient’s inotrope requirements. The kynurenine/tryptophan ratio changed in parallel with the inotrope requirements in our c...