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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. and Ottiger, Manuel and Vögeli, Alaadin and Steuer, Christian and Bernasconi, Luca and Thomann, Robert and Christ-Crain, Mirjam and Henzen, Christoph and Hoess, Claus and Zimmerli, Werner and Huber, Andreas and Mueller, Beat and Schuetz, Philipp. (2017) Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study. Clinical Chemistry and Laboratory Medicine, 55 (7). pp. 1060-1069.

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Official URL: http://edoc.unibas.ch/55128/

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Abstract

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).; 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.; 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.; 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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie (Christ-Crain)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie (Christ-Crain)
UniBasel Contributors:Christ-Crain, Mirjam
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:De Gruyter
ISSN:1434-6621
e-ISSN:1437-4331
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:09 Oct 2017 14:17
Deposited On:04 Oct 2017 08:35

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