P806 Assessment of tryptophan metabolism and cytokine profile in cerebrospinalfiuid samples from patients with bacterial meningitis

Coutinho, Leonam Gomes; Bellac, Caroline L.; Grandgirard, Denis; Wittwer, Matthias; Coimbra, Roney Santos; Christen, Stephan; Agnez-Lima, Lucymara Fassarella; Marinho, L.A.; Leib, L.S.

doi:10.1016/s0924-8579(07)70647-7

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Data suggesting that concentrations of KYN pathway metabolites are significantly altered in human patients with BM compared with controls have already been reported [20]. The KYN pathway is also induced in other diseases associated with inflammation-induced brain injury, such as Huntington's disease [21], schizophrenia [22], multiple sclerosis AIDS-dementia complex and cerebral malaria [23,24].…”

Section: Introductionmentioning

confidence: 99%

“…Accumulation of neurotoxic intermediates of the KYN pathway was observed in the cortex and hippocampus of rats during the early and late phases of acute experimental bacterial meningitis [ 19 ]. Data suggesting that concentrations of KYN pathway metabolites are significantly altered in human patients with BM compared with controls have already been reported [ 20 ]. The KYN pathway is also induced in other diseases associated with inflammation-induced brain injury, such as Huntington's disease [ 21 ], schizophrenia [ 22 ], multiple sclerosis AIDS-dementia complex and cerebral malaria [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis

et al. 2011

View full text Add to dashboard Cite

BackgroundThe kynurenine (KYN) pathway has been shown to be altered in several diseases which compromise the central nervous system (CNS) including infectious diseases such as bacterial meningitis (BM). The aim of this study was to assess single nucleotide polymorphisms (SNPs) in four genes of KYN pathway in patients with meningitis and their correlation with markers of immune response in BM.MethodsOne hundred and one individuals were enrolled in this study to investigate SNPs in the following genes: indoleamine-2,3-dioxygenase (IDO1 gene), kynureninase (KYNU gene), kynurenine aminotransferase I (CCBL1 gene), and kynurenine aminotransferase II (AADAT gene). SNP analyses were performed by primer-introduced restriction analysis-PCR (PIRA-PCR) followed by RFLP. Cytokines were measured using multiplex bead assay while immunoglobulins (IG) by immunodiffusion plates and NF-kappaB and c-Jun by dot blot assay.ResultsThe variant allele of SNP AADAT+401C/T showed prevalent frequency in patients with BM. A significant decrease (p < 0.05) in TNF-α, IL-1β, IL-6, MIP-1αCCL3 and MIP-1β/CCL4 levels was observed in BM patients homozygous (TT) to the SNP AADAT+401C/T. Furthermore, a significant (p < 0.05) decrease in cell count was observed in cerebrospinal fluid (CSF) from patients with TT genotype. In addition, an increase in the IgG level in adults (p < 0.05) was observed. The variant allele for KYNU+715G/A was found with low frequency in the groups, and the SNPs in IDO1+434T/G, KYNU+693G/A, CCBL1+164T/C, and AADAT+650C/T had no frequency in this population.ConclusionsThis study is the first report of an association of SNP AADAT+401C/T with the host immune response to BM, suggesting that this SNP may affect the host ability in recruitment of leukocytes to the infection site. This finding may contribute to identifying potential targets for pharmacological intervention as adjuvant therapy for BM.

show abstract