Tryptophan metabolism to kynurenine is a potential novel contributor to hypotension in human sepsis*

Abstract

: Indoleamine 2,3-dioxygenase 1 is expressed in resistance vessels in human sepsis and Indoleamine 2,3-dioxygenase activity correlates with hypotension in human septic shock. Indoleamine 2,3-dioxygenase 1 is thus a potential novel contributor to hypotension in sepsis.

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

“…This decrease correlated with higher disease severity as measured by higher levels of PCT Brought to you by | Universitaetsbibliothek Basel Authenticated Download Date | 10/9/17 4:17 PM and CRP, and higher risk scores (qSOFA and PSI). These results are in line with previous research [26][27][28]. The physiopathological mechanism of decreasing TRP during infection and inflammation is a matter of current discussion [29].…”

Blockade of Indoleamine 2,3-Dioxygenase Reduces Mortality from Peritonitis and Sepsis in Mice by Regulating Functions of CD11b+Peritoneal Cells

“…In addition, Trp supplementation did not affect the intestinal bacterial growth on the minimal-medium plates (data not shown). These results suggest that CLP induces peritonitis and sepsis in Ido ϩ/ϩ mice, as previously reported (35)(36)(37), and that the bacterial infection is regulated in the local infection focus in Ido Ϫ/Ϫ mice, resulting in the improved survival rate.…”

Role of indoleamine 2,3-dioxygenase in health and disease

“…Clinical and experimental animal studies highlight an important role for IDO1 and the Kyn pathway in response to endotoxic shock. IDO1 expression and activity are increased in septic patients and animals in inflamed cardiac tissue, spleen DCs, bone marrow-derived CD11b + cells and endothelial cells of resistance vessels [125,182,479,480]. Moreover, IDO1 activity measured as the plasma Kyn/L-Trp ratio is significantly elevated in patients with bacteraemia caused by S. aureus, S. pneumoniae, E. coli and β-haemolytic streptococci, with the extent of increase representing an independent predictor of disease severity and death [481,482].…”

“…In humans, IDO1 is induced within the vascular endothelium of disease states such as pre-eclampsia [571], as well as in resistance vessels and cardiac tissue during septic shock in response to various infections including S. aureus, E. coli, Enterobacter cloacae, Serratia marcescens, Legionella pneumophila, Enterococcus spp., Streptococcus spp., and coagulase-negative Staphylcoccus and Klebsiella [479]. In human sepsis, IDO1 expression and activity positively correlates with the degree of hypotension [479].…”