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Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

Meier, Marc A. ; Ottiger, Manuel ; Vögeli, Alaadin ; Steuer, Christian ; Bernasconi, Luca ; Thomann, Robert ; Christ-Crain, Mirjam ; Henzen, Christoph ; Hoess, Claus ; Zimmerli, Werner ; Huber, Andreas ; Mueller, Beat ; Schuetz, Philipp

In: Clinical Chemistry and Laboratory Medicine (CCLM), 2017, vol. 55, no. 7, p. 1060-1069

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    Title
    • Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study
    Author
    • Meier, Marc A.. Medical University Department, Kantonsspital Aarau, Aarau, Switzerland
    • Ottiger, Manuel. Medical University Department, Kantonsspital Aarau, Aarau, Switzerland
    • Vögeli, Alaadin. Medical University Department, Kantonsspital Aarau, Aarau, Switzerland
    • Steuer, Christian. Department of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland
    • Bernasconi, Luca. Department of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland
    • Thomann, Robert. Medical Department, Buergerspital Solothurn, Solothurn, Switzerland
    • Christ-Crain, Mirjam. Medical University Department, University Hospital Basel, Basel, Switzerland
    • Henzen, Christoph. Medical Department, Kantonsspital Luzern, Luzern, Switzerland
    • Hoess, Claus. Medical Department, Kantonsspital Muensterlingen, Muensterlingen, Switzerland
    • Zimmerli, Werner. Medical University Department, Kantonsspital Baselland, Liestal, Switzerland
    • Huber, Andreas. Department of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland
    • Mueller, Beat. Medical University Department, Kantonsspital Aarau, Aarau, Switzerland
    • Schuetz, Philipp. University Department of Medicine, Kantonsspital Aarau, Tellstrasse, CH-5001 Aarau, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Clinical Chemistry and Laboratory Medicine (CCLM), 2017, vol. 55, no. 7, p. 1060-1069. De Gruyter
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:332754
    Summary
    AbstractBackground: As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP). Methods: We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP patients included in a previous multicenter trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We studied their association with inflammation (C-reactive protein), infection (procalcitonin) and clinical outcome. Results: Mortality in the 268 included patients was 45% within 6 years of follow-up. IDO and kynurenine showed a strong positive correlation with markers of infection (procalcitonin) and inflammation (C-reactive protein) as well as sepsis and CAP severity scores. Tryptophan showed similar, but negative correlations. In a multivariate regression analysis adjusted for age and comorbidities, higher IDO activity and lower tryptophan levels were strongly associated with short-term adverse outcome defined as death and/or ICU admission within 30 days with adjusted odds ratios of 9.1 [95% confidence interval (CI) 1.4-59.5, p=0.021] and 0.11 (95% CI 0.02-0.70, p=0.021). Multivariate analysis did not reveal significant associations for kynurenine and serotonin. Conclusions: In hospitalized CAP patients, higher IDO activity and lower tryptophan levels independently predicted disease severity and short-term adverse outcome. Whether therapeutic modulation of IDO has positive effects on outcome needs further investigation.