title: Tryptophan metabolism to kynurenine is a potential novel contributor to hypotension in human sepsis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Prospective, matched, single-center, cohort study.
  
  
  METHODS
  Intensive care unit of a tertiary teaching hospital matched to control subjects from the general medical ward and healthy volunteers.
  
  
  METHODS
  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.
  
  
  METHODS
  None.
  
  
  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.
authors.affiliation: Centre for Vascular Research, School of Medical Sciences (Pathology) and Bosch Institute, Sydney, Australia.
authors.forename: Dechaboon
authors.initials: D
authors.lastname: Changsirivathanathamrong
authors.forename: Yutang
authors.initials: Y
authors.lastname: Wang
authors.forename: Dorrilyn
authors.initials: D
authors.lastname: Rajbhandari
authors.forename: Ghassan J
authors.initials: GJ
authors.lastname: Maghzal
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Mak
authors.forename: Clive
authors.initials: C
authors.lastname: Woolfe
authors.forename: Johan
authors.initials: J
authors.lastname: Duflou
authors.forename: Val
authors.initials: V
authors.lastname: Gebski
authors.forename: Cris G
authors.initials: CG
authors.lastname: dos Remedios
authors.forename: David S
authors.initials: DS
authors.lastname: Celermajer
authors.forename: Roland
authors.initials: R
authors.lastname: Stocker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007022:Hypotension / Q000209:etiology* / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007737:Kynurenine / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010289:Parenteral Nutrition, Total; D011446:Prospective Studies; D012772:Shock, Septic / Q000150:complications* / Q000378:metabolism; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan