title: The kynurenine pathway is involved in bacterial meningitis.
abstract: 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.
  
  
  CONCLUSIONS
  This study suggests a downward modulatory effect of the KP on CSF inflammation during BM.
authors.forename: Leonam G
authors.initials: LG
authors.lastname: Coutinho
authors.forename: Stephan
authors.initials: S
authors.lastname: Christen
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Bellac
authors.forename: Fabrícia Lima
authors.initials: FL
authors.lastname: Fontes
authors.forename: Fladjule Rejane Soares de
authors.initials: FR
authors.lastname: Souza
authors.forename: Denis
authors.initials: D
authors.lastname: Grandgirard
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Leib
authors.forename: Lucymara F
authors.initials: LF
authors.lastname: Agnez-Lima
mesh_terms: D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid*; D007737:Kynurenine / Q000134:cerebrospinal fluid*; D008297:Male; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid*; D055815:Young Adult
chemical_list: D016207:Cytokines; D007737:Kynurenine