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 (rs=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.
Tryptophan degradation in multiple trauma patients: survivors compared with non-survivors
Martin Ploder, Andreas Spittler, Katharina Schroecksnadel, Gabriele Neurauter, Linda E. Pelinka, Erich Roth, Dietmar Fuchs; Tryptophan degradation in multiple trauma patients: survivors compared with non-survivors. Clin Sci (Lond) 1 April 2009; 116 (7): 593–598. doi: https://doi.org/10.1042/CS20080319
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