Accelerated Tryptophan Degradation Predicts Poor Survival in Trauma and Sepsis Patients

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

Tryptophan degradation in multiple trauma patients: survivors compared with non-survivors

International audienceImmune dysfunction in trauma patients is associated with immune system activation and inflammation. Cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO) 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 kynurenine to tryptophan ratio (kyn/trp). This study investigated whether tryptophan degradation is associated with outcome of 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. Of every patient up to 5 specimens within this observation period were included in this analysis, in total 69 specimens were available. For further comparisons, concentrations of immune activation marker neopterin were measured. Compared to healthy controls, average kyn/trp and kynurenine were increased in patients, and tryptophan concentrations were decreased. During follow-up, increasing kyn/trp and kynurenine concentrations (all p <0.001) were observed, the changes of tryptophan concentrations were not significant. Non-survivors presented with higher kyn/trp and with higher kynurenine concentrations than survivors. Kyn/trp correlated with neopterin (rs = 0.590, p <0.001) concentrations. Data imply that increased tryptophan degradation in patients is due to activated IDO, which most likely represents a result of host defence response. Data support a possible role of IDO in the development of immunodeficiency and death in patients