Avaliação de citocinas no sangue periférico e expressão gênica em pacientes com Esclerose Múltipla tratados com Interferon-beta
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2017-09-29
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Universidade Federal de Goiás
Resumo
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.
Descrição
Palavras-chave
Esclerose Múltipla , Interferon-beta , TNF-α , IL-10 , IL-32 , γ , Receptores do tipo Toll , Multiple sclerosis , Interferon-beta , TNF-α , IL-10 , IL-32γ , Toll-like receptors
Citação
OLIVEIRA, Iara Barreto Neves. Avaliação de citocinas no sangue periférico e expressão gênica em pacientes com Esclerose Múltipla tratados com Interferon-beta. 2017. 99 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2017.