Tryptophan degradation in multiple trauma patients: survivors compared with non-survivors.
Immune dysfunction in trauma patients is associated with immune system activation and inflammation. The cytokine-inducible enzyme IDO (indoleamine 2,3-dioxygenase) initiates the degradation of the essential aromatic amino acid tryptophan via the kynurenine pathway and could contribute to deficient immune responsiveness. Activated IDO is indicated by an increased kyn/trp (kynurenine/tryptophan) ratio. The aim of the present study was to investigate whether tryptophan degradation is associated with outcome in patients post-trauma. Tryptophan and kynurenine concentrations were measured by HPLC in serum specimens of 15 patients post-trauma during 12-14 days of follow-up. Up to five samples within this observation period from each patient were included in this analysis, and a total a 69 samples were available. For further comparisons, concentrations of the immune activation marker neopterin were measured. Compared with healthy controls, the average kyn/trp ratio and kynurenine concentrations were increased in patients, whereas tryptophan concentrations were decreased. During follow-up, increased kyn/trp ratio and kynurenine concentrations (all P<0.001) were observed, whereas the changes in tryptophan concentrations were not significant. Non-survivors had higher kyn/trp ratios and kynurenine concentrations compared with survivors. The kyn/trp ratio correlated with neopterin concentrations (r(s)=0.590, P<0.001). In conclusion, these results imply that increased tryptophan degradation in patients is due to activated IDO, which most probably is a consequence of a host defence response. These findings support a possible role for IDO in the development of immunodeficiency and death in patients.
Ploder
Martin
M
Department of Surgery, Medical University of Vienna, Vienna, Austria.
Spittler
Andreas
A
Schroecksnadel
Katharina
K
Neurauter
Gabriele
G
Pelinka
Linda E
LE
Roth
Erich
E
Fuchs
Dietmar
D
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood / Q000502:physiology; D007737:Kynurenine / Q000097:blood; D008297:Male; D008875:Middle Aged; D009104:Multiple Trauma / Q000097:blood* / Q000276:immunology; D011379:Prognosis; D014364:Tryptophan / Q000097:blood*; D055815:Young Adult
D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan