Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/8077
Title: Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy.
Authors: Moens, Britta
Decanine, Daniele
Menezes, Soraya Maria
Khouri, Antonio Ricardo
Santos, Gilvanéia Silva
López, Giovanni
Alvarez, Carolina
Talledo, Michael
Gotuzzo, Eduardo
Kruschewsky, Ramon de Almeida
Castro Filho, Bernardo Galvão
Vandamme, Anne-Mieke
Van Weyenbergh, Johan Jozef Rosa Maria
Affilliation: Rega Institute for Medical Research. K. U. Leuven. Leuven, Belgium
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Rega Institute for Medical Research K. U. Leuven. Leuven, Belgium
Rega Institute for Medical Research. K. U. Leuven. Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, Peru
Rega Institute for Medical Research. K. U. Leuven. Leuven, Belgium / Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, Peru
Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, Peru
Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, Peru / Universidad Peruana Cayetano Heredia. Departamento de Medicina, Facultad de Medicina. Lima, Peru
Bahia School of Medicine and Public Health. Salvador-BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Bahia School of Medicine and Public Health. Salvador-BA, Brasil
Rega Institute for Medical Research. K. U. Leuven. Leuven, Belgium / Universidade Nova de Lisboa. Instituto de Higiene e Medicina Tropical. Centro de Malária e outras Doenças Tropicais. Lisboa, Portugal
Rega Institute for Medical Research. K. U. Leuven. Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Abstract: BACKGROUND: Clear therapeutic guidelines for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are missing due to the lack of randomized double-blind controlled clinical trials. Moderate yet similar clinical benefit has been demonstrated for IFN-α and high-dose ascorbic acid (AA) monotherapy in a large open clinical trial. However, there is a lack of in vivo and in vitro studies exploring and comparing the effects of high-dose AA and IFN-α treatment in the context of HAM/TSP. Therefore, we performed the first comparative analysis of the ex vivo and in vitro molecular and cellular mechanisms of action of IFN-α and high-dose AA in HAM/TSP. PRINCIPAL FINDINGS: Through thymidine incorporation and quantification of Th1/Th2/Th17 cytokines, we demonstrate that high-dose AA displays differential and superior antiproliferative and immunomodulatory effects over IFN-α in HAM/TSP PBMCs ex vivo. In addition, high-dose AA, but not IFN-α, induced cell death in both HAM/TSP PBMCs and HTLV-1-infected T-cell lines MT-2 and MT-4. Microarray data combined with pathway analysis of MT-2 cells revealed AA-induced regulation of genes associated with cell death, including miR-155. Since miR-155 has recently been demonstrated to up-regulate IFN-γ, this microRNA might represent a novel therapeutic target in HAM/TSP, as recently demonstrated in multiple sclerosis, another neuroinflammatory disease. On the other hand, IFN-α selectively up-regulated antiviral and immune-related genes. CONCLUSIONS: In comparison to IFN-α, high-dose AA treatment has superior ex vivo and in vitro cell death-inducing, antiproliferative and immunomodulatory anti-HTLV-1 effects. Differential pathway activation by both drugs opens up avenues for targeted treatment in specific patient subsets.
DeCS: Antineoplásicos/farmacologia
Ácido Ascórbico/farmacologia
Morte Celular/efeitos de drogas
Fatores Imunológicos/farmacologia
Leucemia-Linfoma de Células T do Adulto/quimioterapia
Adulto
Idoso
Células Cultivadas
Feminino
Perfilação da Expressão Gênica
Humanos
Interferon-alfa/farmacologia
Masculino
Análise em Microsséries
Meia-Idade
Técnicas de Cultura de Órgãos
Doenças da Medula Espinal/quimioterapia
Adulto Jovem
Issue Date: 2012
Publisher: Public Library of Science
Citation: MOENS, B. Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. PLoS Neglected Tropical Diseasesa, v. 6, n. 7, p. e1729, 2012.
DOI: 10.1371/journal.pntd.0001729
ISSN: 1935-2735
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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