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

Meier, Marc; Ottiger, Manuel; Vögeli, Alaadin; Bernasconi, Luca; Thomann, Robert V.; Henzen, Christoph; Hoess, Claus; Zimmerli, Werner; Huber, Andreas; Müeller, Beat; Schuetz, Philipp

doi:10.1515/cclm-2016-0912

Cited by 21 publications

(20 citation statements)

References 42 publications

(44 reference statements)

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“…However, no major gender differences in tryptophan metabolism were observed in the never-smoking population, with only kynurenic acid evidencing a small increase in males ( p = 0.04). A few studies have previously reported reduced blood tryptophan levels and increased kynurenine, suggesting an increase in IDO activity in pneumonia patients [30,31]. Elevated IDO activity was also reported in acute exacerbations of COPD at the time of hospitalization, and then shown to return to lower levels at the one month follow-up [13,32].…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of the Tryptophan Pathway Evidences Gender Differences in COPD

et al. 2019

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Increased activity of indoleamine 2,3-dioxygenase (IDO) and tryptophan hydroxylase (TPH) have been reported in individuals with chronic obstructive pulmonary disease (COPD). We therefore investigated the effect of gender stratification upon the observed levels of tryptophan metabolites in COPD. Tryptophan, serotonin, kynurenine, and kynurenic acid were quantified in serum of never-smokers (n = 39), smokers (n = 40), COPD smokers (n = 27), and COPD ex-smokers (n = 11) by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). The individual metabolite associations with lung function, blood, and bronchoalveolar lavage (BAL) immune-cell composition, as well as chemokine and cytokine levels, were investigated. Stratification by gender and smoking status revealed that the observed alterations in kynurenine and kynurenic acid, and to a lesser extent serotonin, were prominent in males, irrespective of COPD status (kynurenine p = 0.005, kynurenic acid p = 0.009, and serotonin p = 0.02). Inferred serum IDO activity and kynurenine levels decreased in smokers relative to never-smokers (p = 0.005 and p = 0.004, respectively). In contrast, inferred tryptophan hydroxylase (TPH) activity and serotonin levels showed an increase with smoking that reached significance with COPD (p = 0.01 and p = 0.01, respectively). Serum IDO activity correlated with blood CXC chemokine ligand 9 (CXCL9, p = 0.0009, r = 0.93) and chemokine (C-C motif) ligand 4 (CCL4.(p = 0.04, r = 0.73) in female COPD smokers. Conversely, serum serotonin levels correlated with BAL CD4+ T-cells (%) (p = 0.001, r = 0.92) and CD8+ T-cells (%) (p = 0.002, r = −0.90) in female COPD smokers, but not in male COPD smokers (p = 0.1, r = 0.46 and p = 0.1, r = −0.50, respectively). IDO- and TPH-mediated tryptophan metabolites showed gender-based associations in COPD, which were primarily driven by smoking status.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of the Tryptophan Pathway Evidences Gender Differences in COPD

et al. 2019

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“…Androgens have already been linked to the severity of COVID-19 as possible mechanisms driving disease outcomes 20 . Steroid, proteasome, and tryptophan metabolisms are linked to viral infections and subsequent host immune response [21][22][23] . Moreover, monocyte and macrophage activation has been linked to the hyperin ammatory phenotypes in SARS-CoV-2 infection that have adverse clinical outcomes 24 .…”

Section: Discussionmentioning

confidence: 99%

In silico Drug Repurposing to combat COVID-19 based on Pharmacogenomics of Patient Transcriptomic Data

Das

Camphausen

Shankavaram

2020

Preprint

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The ongoing global pandemic of coronavirus disease 2019 (COVID-19) continues to affect a growing number of populations in different parts of the world. In the current situation, drug repurposing is a viable strategy to combat COVID-19. The drugs targeting the host receptors that interact with SARS-CoV-2 are possible candidates. However, assessment of their effectiveness in COVID-19 patients is necessary before prioritizing them for further study. We attempted to shortlist the candidate drugs using an in-silico approach. First, we analysed two published transcriptomic data sets of COVID-19- and SARS-infected patients compared to healthy individuals to find the key pathways altered after infection. Then, using publicly available drug perturbational data sets in human cell lines from the Broad Institute Connectivity Map (CMAP), we assessed the effects of the approved drugs on the altered pathways. We also used the available pharmacogenomic data sets from the Genomics of Drug Sensitivity in Cancer (GDSC) portal to assess the effects of the altered pathways on resistance or sensitivity to the drugs in human cell lines. Our analysis identified many candidate drugs, some of which are already being investigated for treatment of COVID-19 and can serve as a basis for prioritizing additional viable candidate drugs for COVID-19.

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“…The HIAA did not correlate with coronary occlusion but it had a significant difference with the CHD group, because pneumonia and sepsis were suggested as causes of death in the control group. Infection state might decrease plasma serotonin, the substrate of HIAA, by inhibiting serotonin transporter in platelets [31].…”

Section: Discussionmentioning

confidence: 99%

Possible Use of Blood Tryptophan Metabolites as Biomarkers for Coronary Heart Disease in Sudden Unexpected Death

et al. 2019

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Coronary heart disease (CHD) is the major cause of death in sudden unexpected death (SUD) cases. Tryptophan (TRP) and its metabolites are correlated with the CHD patient but less studies in the SUD. The aim of this study was to evaluate the relationship of TRP and its metabolites with the CHD in the SUD cases. Blood samples and heart tissues were collected from CHD subjects (n = 31) and the control group (n = 72). Levels of kynurenine (KYN), kynurenic acid (KYA), xanthurenic acid (XAN), 3-hydroxyanthranillic acid (HAA), quinolinic acid (QA), picolinic acid (PA) and 5-hydroxyindoleacetic acid (HIAA) were determined by HPLC-DAD. A severity of heart occlusion was categorized into four groups, and the relationship was measured with the TRP metabolites. The HIAA and The KYN levels significantly differed (p < 0.01) between the CHD group and the control group. Lower levels of QA/XAN, PA/KA, HAA/XAN, KYN/XAN and KYN/TRP were found in the CHD group. However, PA/HAA, PA/HIAA, PA/KYN and XAN/KA values in the CHD group were higher than the control group (p < 0.05). This study revealed that the values of PA/KA and PA/HAA provided better choices for a CHD biomarker in postmortem bodies.

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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

Cited by 21 publications

References 42 publications

Dysregulation of the Tryptophan Pathway Evidences Gender Differences in COPD

Dysregulation of the Tryptophan Pathway Evidences Gender Differences in COPD

In silico Drug Repurposing to combat COVID-19 based on Pharmacogenomics of Patient Transcriptomic Data

Possible Use of Blood Tryptophan Metabolites as Biomarkers for Coronary Heart Disease in Sudden Unexpected Death

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