Accelerated Tryptophan Degradation in Trauma and Sepsis Patients is Related to Pro-inflammatory Response and to the Diminished in vitro Response of Monocytes

Pteridines

Ploder Martin¹  Neurauter Gabriele²  Schroecksnadel Katharina²  Fuchs Dietmar³  Pelinka Linda E.⁴  Spittler Andreas⁵  Roth Erich⁵ 

[1] Department of Surgery, Medical University of Vienna;Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria;Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Fritz Pregl Strasse 3, Innsbruck, Austria, Phone: [phone], Fax: [phone];Ludwig Boltzmann Institute for Experimental and Clinical Traumatology;Research Center for Traumatology AUVA, Vienna, Austria;

关键词: tryptophan;    kynurenine;    indoleamine (2,3)-dioxygenase;    neopterin;    interleukin-6;    tumor necrosis factor-α;    trauma;    sepsis;    survival;   

DOI  :  10.1515/pteridines.2009.20.1.54

来源: DOAJ

【 摘 要 】

Immune system activation and inflammation accompanies immune dysfunction in trauma and sepsis patients. Tryptophan degradation via the kynurenine pathway by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO) could contribute to the deficient responsiveness of immunocompetent cells. Activated IDO in patients after trauma and with sepsis is indicated by an increased kynurenine to tryptophan ratio (kyn/trp), which was found to be associated with poor outcome of patients. In this study, tryptophan and kynurenine concentrations in 18 patients post trauma or with sepsis during 12-14 days of follow up (up to 84 specimens were available) were compared to concentrations of neopterin and cytokines tumor necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) and the in vitro response of lipopolysaccharide-stimulated monocytes. Compared to healthy controls, average kyn/trp and kynurenine, TNF-α, IL-6 and neopterin concentrations were increased in patients, and tryptophan concentrations were decreased. During follow-up, only kyn/trp, kynurenine and neopterin concentrations (all p <0.001) were increasing, whereas the changes of tryptophan, TNF-α and IL-6 concentrations were not significant. Non-survivors presented not only with higher kyn/trp and with higher kynurenine and neopterin concentrations than survivors, but also TNF-α and IL-6 concentrations were higher. Kyn/trp correlated with neopterin (rs = 0.590; p <0.001) and also with TNF-α (rs = 0.374; p <0.01) and IL-6 concentrations (rs = 0.262; p <0.05) and inversely with the in vitro response of stimulated monocytes. Data imply that increased tryptophan degradation in patients post trauma is due to IDO activation. Increased IDO activity most likely represents a result of host defence response in patients, and data support a possible role of IDO to diminish immunoresponsiveness in such patients.

【 授权许可】

Unknown