Fingolimod Increases Brain-Derived Neurotrophic Factor Level Secretion from Circulating T Cells of Patients with Multiple Sclerosis.
CNS Drugs
; 33(12): 1229-1237, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31713782
ABSTRACT
BACKGROUND:
The pathophysiology of multiple sclerosis involves an autoimmune and a neurodegenerative mechanism. Central nervous system-infiltrating immune cells in multiple sclerosis also possess a neuroprotective activity through secretion of neurotrophins, such as brain-derived neurotrophic factor. Fingolimod was shown to slow the progression of disability and loss of brain volume.OBJECTIVE:
The objective of this study was to explore whether fingolimod induces secretion of neurotrophins by immune cells.METHODS:
Blood was drawn from 21 patients before the initiation of treatment with fingolimod and at 6 and 12 months of follow-up. The levels of the neurotrophic factors brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, ß-nerve growth factor, neurotrophin-3, neurotrophin-4, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor were screened in the supernatants of separated T cells and monocyte cultures using a customized, multiplex enzyme-linked immunosorbent assay. Brain-derived neurotrophic factor levels were further validated by a specific enzyme-linked immunosorbent assay.RESULTS:
Treatment with fingolimod significantly increased brain-derived neurotrophic factor secretion from T cells. A specific enzyme-linked immunosorbent assay confirmed these results in the supernatant of T cells after 6 and 12 months of therapy.CONCLUSIONS:
T cells that reach the bloodstream of fingolimod-treated patients with multiple sclerosis may contribute to the neuroprotective effect of this therapy by increased secretion of brain-derived neurotrophic factor. This mechanism of action of fingolimod in patients with multiple sclerosis has not been previously reported.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Fator Neurotrófico Derivado do Encéfalo
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Cloridrato de Fingolimode
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Esclerose Múltipla
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
CNS Drugs
Ano de publicação:
2019
Tipo de documento:
Article