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

Early Increase of Plasma Homocysteine in Sepsis Patients with Poor Outcome

Moderate hyperhomocysteinemia is a well-established coronary risk factor that develops when dietary supply with folate and/or vitamin B12 is inadequate. Recently, stimulated peripheral blood mononuclear cells were shown to produce homocysteine. Thus, the stimulated immune system may contribute to moderate hyperhomocysteinemia during certain diseases. Because multiple trauma and sepsis are accompanied by often strong inflammatory responses, we investigated whether hyperhomocysteinemia may develop in patients. Total homocysteine and cysteine concentrations were measured in 83 plasma specimens from 18 patients (14 men, 4 women; 15 posttrauma with sepsis and 3 with sepsis alone) every third day of follow-up. Finally results were compared with concentrations of cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6, the immune activation marker neopterin and the extent of tryptophan degradation as indicated by the kynurenine-to-tryptophan ratio (kyn/trp). Compared with baseline, average total homocysteine (P < 0.05, d 4–d 10) and cysteine (P < 0.05, d 7–d 13) concentrations increased during follow-up of patients. However, only the increase of homocysteine was related to the survival status: total homocysteine was significantly higher in nonsurvivors (P < 0.05, d 4 and d 10) than in survivors, whereas cysteine concentrations increased in both subgroups. Homocysteine correlated with kyn/trp but not with neopterin concentrations. Increase of total homocysteine is common in patients after trauma with unfavorable outcome. Because all patients received standardized enteral nutrition after the end of hypodynamic shock, inconsistent vitamin supply is unlikely to be the reason for hyperhomocysteinemia in some of the patients; rather, it is associated with a stronger proinflammatory response. Certainly, the number of patients in our study is still small and results can only be regarded as preliminary