title: High activity of indoleamine 2,3 dioxygenase enzyme predicts disease severity and case fatality in bacteremic patients.
abstract: Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan (trp) catabolism, may play a critical role in various inflammatory disorders. Recent studies on trauma patients have suggested that the degradation of trp is associated with the development of sepsis. The role of IDO activity in bacteremic patients is unclear. We studied IDO activity in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic streptococcae, or Eschericia coli. The serum concentrations of trp and its metabolite kynurenine (kyn) were measured by reverse-phase high-performance liquid chromatography 1 to 4 days after the positive blood culture and on recovery. The kyn-to-trp ratio (kyn/trp), reflecting the activity of the IDO enzyme, was calculated. The maximum value in the ratio for every patient during 1 to 4 days after positive blood culture was used in analysis. The maximum kyn/trp ratio was significantly higher in nonsurvivors versus those who survived (193.7 vs. 82.4 micromol/mmol; P = 0.001). The AUC(ROC) of maximal kyn/trp in the prediction of case fatality was 0.75 (95% confidence interval, 0.64-0.87), and the kyn/trp ratio at a cutoff level of 120 micromol/mmol showed 83% sensitivity and 69% specificity for fatal disease. A kyn/trp ratio greater than 120 micromol/mmol was associated with increased risk of death versus low (<or=120 micromol/mmol) ratios (odds ratio, 10.8; confidence interval, 3.0-39.8). High IDO activity also remained an independent risk factor for case fatality in a multivariate model adjusted for potential confounders. The data in this report demonstrate that IDO activity is markedly increased in bacteremia patients, constituting an independent predictor of severe disease and case fatality.
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, University of Tampere Medical School, University of Tampere, Tampere, Finland. Reetta.Huttunen@uta.fi
authors.forename: Reetta
authors.initials: R
authors.lastname: Huttunen
authors.forename: Jaana
authors.initials: J
authors.lastname: Syrjänen
authors.forename: Janne
authors.initials: J
authors.lastname: Aittoniemi
authors.forename: Simo S
authors.initials: SS
authors.lastname: Oja
authors.forename: Annika
authors.initials: A
authors.lastname: Raitala
authors.forename: Janne
authors.initials: J
authors.lastname: Laine
authors.forename: Marja
authors.initials: M
authors.lastname: Pertovaara
authors.forename: Risto
authors.initials: R
authors.lastname: Vuento
authors.forename: Heini
authors.initials: H
authors.lastname: Huhtala
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D016470:Bacteremia / Q000097:blood* / Q000201:enzymology* / Q000401:mortality; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007737:Kynurenine / Q000097:blood; D008297:Male; D008875:Middle Aged; D014364:Tryptophan / Q000097:blood; D055815:Young Adult
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan