The kynurenine pathway is involved in bacterial meningitis.

Coutinho, Leonam G; Christen, Stephan; Bellac, Caroline L; Fontes, Fabrícia; de Souza, Fladjule; Grandgirard, Denis; Leib, Stephen; Agnez-Lima, Lucymara F (2014). The kynurenine pathway is involved in bacterial meningitis. Journal of neuroinflammation, 11(169), p. 169. BioMed Central 10.1186/s12974-014-0169-4

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BackgroundBacterial 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.MethodsThe 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.ResultsIn CSF from patients with BM, elevated levels of KYN, KYNA, AA, IDO activity and cytokines were observed. The cytokines INF-¿ and IL-1Ra showed a positive correlation with IDO activity, and TNF-¿ 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.ConclusionThis study suggests a downward modulatory effect of the KP on CSF inflammation during BM.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Other Institutions > Teaching Staff, Faculty of Medicine

UniBE Contributor:

Grandgirard, Denis and Leib, Stephen

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1742-2094

Publisher:

BioMed Central

Funders:

[UNSPECIFIED] UBS Optimus Foundation

Language:

English

Submitter:

Stephen Leib

Date Deposited:

06 Feb 2015 13:35

Last Modified:

08 Feb 2017 14:40

Publisher DOI:

10.1186/s12974-014-0169-4

PubMed ID:

25274277

BORIS DOI:

10.7892/boris.61931

URI:

https://boris.unibe.ch/id/eprint/61931

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