title: Accelerated tryptophan degradation predicts poor survival in trauma and sepsis patients.
abstract: Immune system activation and inflammation accompanies immune dysfunction in trauma and sepsis patients. Immunodeficiency may develop in such patients as one consequence of an activated chronic pro-inflammatory response. According to recent data, degradation of L-tryptophan (TRP) via the kynurenine (KYN) pathway by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO) could represent an important contributor to the deficient responsiveness of immunocompetent cells. Compared to healthy controls, patients post trauma or with sepsis had increasing KYN concentrations and KYN to TRP ratios (KYN/TRP) whereas TRP concentrations decreased. Likewise, concentrations of cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and of immune activation marker neopterin increased in patients (all p < 0.001). Furthermore in patients KYN/TRP, KYN and neopterin concentrations were further increasing (all p < 0.001), whereas the changes of TRP, TNF-α and IL-6 concentrations were not significant. Compared to the survivors, the non-survivors had a higher concentration of KYN, neopterin, TNF-α and IL-6 as well as a higher KYN/TRP ratio. KYN/TRP correlated with neopterin (p < 0.001) and also with TNF-α (p < 0.01) and IL-6 concentrations (p < 0.05) and inversely with the in vitro response of stimulated monocytes. We conclude that increased TRP degradation in patients post trauma is closely associated with immune activation. Cytokines released during the pro-inflammatory response may induce the activity of IDO and thus accelerate TRP degradation. Thus, increased IDO activity most likely represents a result of host response to pro-inflammation in patients. Data support a possible role of inflammation-induced IDO in the diminished immunoresponsiveness in patients.
authors.affiliation: Department of Surgery, Medical University of Vienna.
authors.forename: Martin
authors.initials: M
authors.lastname: Ploder
authors.forename: Andreas
authors.initials: A
authors.lastname: Spittler
authors.forename: Katharina
authors.initials: K
authors.lastname: Kurz
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neurauter
authors.forename: Linda E
authors.initials: LE
authors.lastname: Pelinka
authors.forename: Erich
authors.initials: E
authors.lastname: Roth
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
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