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The kynurenine pathway is involved in bacterial meningitis

BACKGROUND: Bacterial meningitis (BM) is characterized by an intense host inflammatory reaction, which contributes to the development of brain damage and neuronal sequelae. Activation of the kynurenine (KYN) pathway (KP) has been reported in various neurological diseases as a consequence of inflamma...

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Autores principales: Coutinho, Leonam G, Christen, Stephan, Bellac, Caroline L, Fontes, Fabrícia Lima, de Souza, Fladjule Rejane Soares, Grandgirard, Denis, Leib, Stephen L, Agnez-Lima, Lucymara F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189685/
https://www.ncbi.nlm.nih.gov/pubmed/25274277
http://dx.doi.org/10.1186/s12974-014-0169-4
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author Coutinho, Leonam G
Christen, Stephan
Bellac, Caroline L
Fontes, Fabrícia Lima
de Souza, Fladjule Rejane Soares
Grandgirard, Denis
Leib, Stephen L
Agnez-Lima, Lucymara F
author_facet Coutinho, Leonam G
Christen, Stephan
Bellac, Caroline L
Fontes, Fabrícia Lima
de Souza, Fladjule Rejane Soares
Grandgirard, Denis
Leib, Stephen L
Agnez-Lima, Lucymara F
author_sort Coutinho, Leonam G
collection PubMed
description BACKGROUND: Bacterial meningitis (BM) is characterized by an intense host inflammatory reaction, which contributes to the development of brain damage and neuronal sequelae. Activation of the kynurenine (KYN) pathway (KP) has been reported in various neurological diseases as a consequence of inflammation. Previously, the KP was shown to be activated in animal models of BM, and the association of the SNP AADAT + 401C/T (kynurenine aminotransferase II - KAT II) with the host immune response to BM has been described. The aim of this study was to investigate the involvement of the KP during BM in humans by assessing the concentrations of KYN metabolites in the cerebrospinal fluid (CSF) of BM patients and their relationship with the inflammatory response compared to aseptic meningitis (AM) and non-meningitis (NM) groups. METHODS: The concentrations of tryptophan (TRP), KYN, kynurenic acid (KYNA) and anthranilic acid (AA) were assessed by HPLC from CSF samples of patients hospitalized in the Giselda Trigueiro Hospital in Natal (Rio Grande do Norte, Brazil). The KYN/TRP ratio was used as an index of indoleamine 2,3-dioxygenase (IDO) activity, and cytokines were measured using a multiplex cytokine assay. The KYNA level was also analyzed in relation to AADAT + 401C/T genotypes. RESULTS: In CSF from patients with BM, elevated levels of KYN, KYNA, AA, IDO activity and cytokines were observed. The cytokines INF-γ and IL-1Ra showed a positive correlation with IDO activity, and TNF-α and IL-10 were positively correlated with KYN and KYNA, respectively. Furthermore, the highest levels of KYNA were associated with the AADAT + 401 C/T variant allele. CONCLUSION: This study suggests a downward modulatory effect of the KP on CSF inflammation during BM.
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spelling pubmed-41896852014-10-09 The kynurenine pathway is involved in bacterial meningitis Coutinho, Leonam G Christen, Stephan Bellac, Caroline L Fontes, Fabrícia Lima de Souza, Fladjule Rejane Soares Grandgirard, Denis Leib, Stephen L Agnez-Lima, Lucymara F J Neuroinflammation Research BACKGROUND: Bacterial meningitis (BM) is characterized by an intense host inflammatory reaction, which contributes to the development of brain damage and neuronal sequelae. Activation of the kynurenine (KYN) pathway (KP) has been reported in various neurological diseases as a consequence of inflammation. Previously, the KP was shown to be activated in animal models of BM, and the association of the SNP AADAT + 401C/T (kynurenine aminotransferase II - KAT II) with the host immune response to BM has been described. The aim of this study was to investigate the involvement of the KP during BM in humans by assessing the concentrations of KYN metabolites in the cerebrospinal fluid (CSF) of BM patients and their relationship with the inflammatory response compared to aseptic meningitis (AM) and non-meningitis (NM) groups. METHODS: The concentrations of tryptophan (TRP), KYN, kynurenic acid (KYNA) and anthranilic acid (AA) were assessed by HPLC from CSF samples of patients hospitalized in the Giselda Trigueiro Hospital in Natal (Rio Grande do Norte, Brazil). The KYN/TRP ratio was used as an index of indoleamine 2,3-dioxygenase (IDO) activity, and cytokines were measured using a multiplex cytokine assay. The KYNA level was also analyzed in relation to AADAT + 401C/T genotypes. RESULTS: In CSF from patients with BM, elevated levels of KYN, KYNA, AA, IDO activity and cytokines were observed. The cytokines INF-γ and IL-1Ra showed a positive correlation with IDO activity, and TNF-α and IL-10 were positively correlated with KYN and KYNA, respectively. Furthermore, the highest levels of KYNA were associated with the AADAT + 401 C/T variant allele. CONCLUSION: This study suggests a downward modulatory effect of the KP on CSF inflammation during BM. BioMed Central 2014-10-02 /pmc/articles/PMC4189685/ /pubmed/25274277 http://dx.doi.org/10.1186/s12974-014-0169-4 Text en © Coutinho et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Coutinho, Leonam G
Christen, Stephan
Bellac, Caroline L
Fontes, Fabrícia Lima
de Souza, Fladjule Rejane Soares
Grandgirard, Denis
Leib, Stephen L
Agnez-Lima, Lucymara F
The kynurenine pathway is involved in bacterial meningitis
title The kynurenine pathway is involved in bacterial meningitis
title_full The kynurenine pathway is involved in bacterial meningitis
title_fullStr The kynurenine pathway is involved in bacterial meningitis
title_full_unstemmed The kynurenine pathway is involved in bacterial meningitis
title_short The kynurenine pathway is involved in bacterial meningitis
title_sort kynurenine pathway is involved in bacterial meningitis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189685/
https://www.ncbi.nlm.nih.gov/pubmed/25274277
http://dx.doi.org/10.1186/s12974-014-0169-4
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