Document Detail

Tryptophan metabolism to kynurenine is a potential novel contributor to hypotension in human sepsis.
MedLine Citation:
PMID:  21765346     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: To determine whether tryptophan metabolism to kynurenine contributes to the direct regulation of vascular tone in human septic shock.
BACKGROUND: Indoleamine 2,3-dioxygenase 1 is an inducible enzyme that converts tryptophan to kynurenine and shares functional similarities with inducible nitric oxide synthase. Recently, kynurenine has been identified as an endothelium-derived relaxing factor produced during inflammation, raising the possibility that this novel pathway may contribute to hypotension in human sepsis.
DESIGN: Prospective, matched, single-center, cohort study.
SETTINGS: Intensive care unit of a tertiary teaching hospital matched to control subjects from the general medical ward and healthy volunteers.
SUBJECTS: Patients (n = 16) with septic shock had indoleamine 2,3-dioxygenase activity assessed as the kynurenine-to-tryptophan ratio, and the severity of hypotension was determined by their inotrope requirements. Healthy and blood pressure-matched nonseptic control subjects were also studied.
MEASUREMENTS AND MAIN RESULTS: Tissues from septic and control patients were stained for the presence of indoleamine 2,3-dioxygenase 1. Indoleamine 2,3-dioxygenase activity increased up to ninefold in patients with septic shock and was significantly higher than in the two control groups (p < .01). Indoleamine 2,3-dioxygenase activity was strongly correlated with inotrope requirements (p < .001). Indoleamine 2,3-dioxygenase protein was expressed in inflamed cardiac tissue as well as in endothelial cells of resistance vessels in hearts and kidneys from subjects who died from sepsis.
CONCLUSIONS: : 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.
Dechaboon Changsirivathanathamrong; Yutang Wang; Dorrilyn Rajbhandari; Ghassan J Maghzal; Wendy M Mak; Clive Woolfe; Johan Duflou; Val Gebski; Cris G dos Remedios; David S Celermajer; Roland Stocker
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  39     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-18     Completed Date:  2012-01-13     Revised Date:  2012-07-06    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2678-83     Citation Subset:  AIM; IM    
Centre for Vascular Research, School of Medical Sciences (Pathology) and Bosch Institute, Sydney, Australia.
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MeSH Terms
Aged, 80 and over
Hypotension / etiology*,  metabolism
Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
Inflammation / metabolism
Kynurenine / biosynthesis*,  blood,  physiology
Middle Aged
Parenteral Nutrition, Total
Prospective Studies
Shock, Septic / complications*,  metabolism
Tryptophan / blood,  metabolism*
Young Adult
Reg. No./Substance:
343-65-7/Kynurenine; 73-22-3/Tryptophan; EC 2,3,-Dioxygenase
Comment In:
Crit Care Med. 2011 Dec;39(12):2767-9   [PMID:  22094509 ]
Crit Care Med. 2012 Jun;40(6):2006; author reply 2006-7   [PMID:  22610234 ]

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