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Previous issue date: 2008-03-18 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Activation of the kynurenine (KYN) pathway (KP) by modulators of immune system has been observed during several neurological diseases. Here we assessed the association of chemo-/cytokine levels with the concentration of KP metabolites in cerebrospinal fluid (CSF) and plasma samples from patients with bacterial meningitis (BM). All samples were collected from 42 patients diagnosed with acute bacterial
meningitis (ABM), aseptic meningitis, tuberculous meningitis and patients without infection neurological disorders. CSF and plasma concentration of metabolites from the KP was assessed by high pressure liquid chromatography (HPLC) and cytokines
and chemokines by Bio-plex 200 suspension array system. Concentrations of the KP metabolites KYN and kynurenic acid (KYNA) were significantly higher in CSF of patients with ABM compared to other groups. Tryptophan (TRP), anthranilic acid (AA), 3-hydroxykynurenine (3HK) and 3-hydroxyanthranilic acid (3HAA) did not show statistical significance, although some of them presented a good accumulation during ABM. The expression of TNF-alpha, IL-6, IL-1beta, IFN-gamma, IL-10, IL-1 receptor antagonist (IL-1Ra), MIP-1alpha, MIP-1beta, MCP-1 and G-CSF was about 100-fold higher in CSF from ABM patients than other infected groups. In all CSF and plasma samples, the concentration of IL-2, IL-12(p70), IL-4, IL-8 and GM-CSF was not significant. ABM still showed significant concentrations of IL-6, IL-10, IL-1Ra and MCP-1 in plasma samples. Based on the comparison of KP metabolites concentrations between plasma and CSF samples we conclude that the activation of the tryptophan pathway upon BM occurs within the brain. This increase in KP metabolites is most due to activation of the KP by molecules as IFN-gamma and TNF-alpha in response to infection. / A ativa??o da rota da quinurenina por moduladores do sistema imune tem sido observada durante diversas doen?as neurol?gicas. Neste trabalho foi avaliado a associa??o entre os n?veis de citocinas e quimiocinas com a concentra??o dos metab?litos da rota da quinurenina ( Kynurenine pathway KP) em amostras de l?quor e plasma de pacientes com meningite bacteriana. Todas as amostras foram coletadas de 42 pacientes hospitalizados com o diagn?stico de meningites bacteriana aguda, tubercul?sica, ass?ptica e pacientes cujo diagn?stico excluiu infec??o no sistema nervoso central. As concentra??es dos metab?litos da
quinurenina foram avaliadas pela cromatografia l?quida de alta press?o enquanto os n?veis de citocinas e quimiocinas foram medidos pelo Bio-plex 200 suspension array system. Concentra??es de quinurenina e ?cido quinur?nico foram significativamente mais elevadas no l?quor de pacientes com meningite bacteriana aguda do que nos
outros grupos. Ainda no l?quor, os n?veis de triptofano, ?cido antran?lico, 3-hidroxiquinurenina e ?cido 3-hidroxiantran?lico n?o mostraram signific?ncia estat?stica, embora alguns deles apresentaram um bom ac?mulo durante meningite bacteriana aguda. No l?quor dos pacientes com meningite bacteriana foram observados n?veis mais elevados de TNF-alfa, IL-6, IL-1beta, IFN-gama, IL-10, IL-1Ra, MIP-1alpha, MIP-1beta, MCP-1 e G-CSF do que os outros grupos infectados. Em todas as amostras, as concentra??es de IL-2, IL-12(p70), IL-4, IL-8 e GM-CSF n?o variaram significativamente. No grupo com meningite bacteriana aguda foram tamb?m observadas elevadas concentra??es de IL-6, IL-10, IL-1Ra e MCP-1 no plasma. Baseado na compara??o das concentra??es dos metab?litos da via
quinurenina no l?quor e no plasma, conclui-se que a ativa??o desta via metab?lica durante a meningite ocorre primordialmente dentro do c?rebro. O aumento na
concentra??o dos metab?litos da quinurenina durante a infec??o deve-se ativa??o da enzima idoleamina 2,3 dioxigenase por prote?nas da resposta imune hospedeira
principalmente pelo IFN-gama, IL1beta e TNF-alfa.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/16760 |
| Date | 18 March 2008 |
| Creators | Coutinho, Leonam Gomes |
| Contributors | CPF:00297997750, http://lattes.cnpq.br/1083882171718362, Checchinato, C?tia Mendes Pereira, CPF:01880214307, http://lattes.cnpq.br/4124165196694369, Jer?nimo, Selma Maria Bezerra, CPF:15603016434, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4785584A3&dataRevisao=null, Lima, Lucymara Fassarela Agnez |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Gen?tica e Biologia Molecular, UFRN, BR, Gen?tica e Biologia Molecular |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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