Avaliação de citocinas no sangue periférico e expressão gênica em pacientes com Esclerose Múltipla tratados com Interferon-beta

• Ano de defesa: 2017
• Autor(a) principal: Oliveira, Iara Barreto Neves
• Orientador(a): Diniz, Denise Sisterolli
• Banca de defesa: Diniz, Denise Sisterolli, Dias, Fátima Ribeiro, Molinari-Madlum, Eugênia Emília Walquíria Inês
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Programa de Pós-graduação em Ciências da Saúde (FM)
• Departamento: Faculdade de Medicina - FM (RG)
• País: Brasil
• Palavras-chave em Português: Esclerose Múltipla; Interferon-beta; TNF-α; IL-10; IL-32; γ; Receptores do tipo Toll
• Palavras-chave em Inglês: Multiple sclerosis; Interferon-beta; TNF-α; IL-10; IL-32γ; Toll-like receptors
• Área do conhecimento CNPq: CIENCIAS DA SAUDE::MEDICINA
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/7851

Introduction. Multiple Sclerosis (MS) is a Central Nervous System disease, mediated by the Immune System, whose symptoms occur in episodes of relapses. Interferon-beta (IFN-β) is considered a safe treatment for the reduction of relapses, but its mechanisms of action have not yet been clear. Studies have shown involvement of tumor necrosis factor alpha (TNF-α) and of Interleukin-10 (IL-10) in the immunopathogenesis of MS. The role of IL-32, a proinflammatory cytokine has role on several chronic inflammatory diseases, was not elucidated in MS. The effect of IFN-β on these cytokines and disease severity, as measured by the Expanded Disability Status Scale (EDSS), has not yet been established. Objective. The objective of the present study was to evaluate TNF-α, IL-10 and IL-32γ concentrations in the peripheral blood and gene expression of patients with IFN-β. Methods. The sample were patients of the Department of Neurology of the Clinics Hospital of the Federal University, and healthy individuals. Blood collection, blood culture with lipopolysaccharide (LPS), Toll 4 receptor agonist (TLR4), and PAM3Cys, TLR2 agonist, and the quantification of cytokines by real-time polymerase chain reaction were performed. Mann Whitney tests were used for statistical analysis of unpaired data, Wilcoxon for paired samples and Spearman's correlation test, adopting significance level p <0.05. Results. Of the 30 MS patients, 19 were treated with IFN-β and 11, untreated, with a mean age of 40.52 and 42 years, respectively, and female prevalence. TNF-α did not differ between groups but it was less produced after stimulation with Pam3Cys in treated patients compared to controls and untreated patients. IL- 10 concentrations were higher in cultures with LPS in patients treated compared to healthy controls. The mean EDSS of patients treated with IFN-β and untreated did not differ, and the correlation between and TNF-α and IL-10 concentrations produced in blood cultures and EDSS was not significant in the patients. There was a significant correlation between TNF-α concentrations and disease time in untreated patients in non-stimulated cultures and those with TLR2 agonist stimulus. Gene expression of IL-32γ was higher in IFN-β treated patients compared to controls. The gene expression of cytokines correlated positively and significantly in patients and controls and the IL-10 expression was correlated negative e significantly with the disease time in untreated patients. Conclusions. IFN-β reduced patients' response to Pam3Cys. IL-10 was higher in treated patients relative to controls. The correlations were not conclusive about the possible association between these cytokines and the clinic parameters of the disease. IL-32γ was higher in patients treated with IFN-β than in healthy subjects.