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Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy

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dc.contributor.author Moens, B.
dc.contributor.author Decanine, D.
dc.contributor.author Menezes, S.M.
dc.contributor.author Khouri, R.
dc.contributor.author Silva-Santos, G.
dc.contributor.author Lopez, G.
dc.contributor.author Alvarez, C.
dc.contributor.author Talledo Albujar, Michael John
dc.contributor.author Gotuzzo Herencia, José Eduardo
dc.contributor.author de Almeida Kruschewsky, R.
dc.contributor.author Galvão-Castro, B.
dc.contributor.author Vandamme, A.-M.
dc.contributor.author van Weyenbergh, J.
dc.date.accessioned 2022-01-18T19:34:38Z
dc.date.available 2022-01-18T19:34:38Z
dc.date.issued 2012
dc.identifier.uri https://hdl.handle.net/20.500.12866/11078
dc.description.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. en_US
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.ispartofseries PLoS Neglected Tropical Diseases
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Humans en_US
dc.subject comparative study en_US
dc.subject controlled study en_US
dc.subject in vitro study en_US
dc.subject nucleotide sequence en_US
dc.subject flow cytometry en_US
dc.subject gamma interferon en_US
dc.subject HTLV 1 associated myelopathy en_US
dc.subject peripheral blood mononuclear cell en_US
dc.subject Th1 cell en_US
dc.subject Th2 cell en_US
dc.subject tropical spastic paraparesis en_US
dc.subject human cell en_US
dc.subject signal transduction en_US
dc.subject upregulation en_US
dc.subject drug effect en_US
dc.subject interleukin 10 en_US
dc.subject interleukin 2 en_US
dc.subject interleukin 4 en_US
dc.subject interleukin 6 en_US
dc.subject tumor necrosis factor alpha en_US
dc.subject Cells, Cultured en_US
dc.subject leukocyte count en_US
dc.subject immunomodulation en_US
dc.subject antineoplastic agent en_US
dc.subject alpha interferon en_US
dc.subject T cell leukemia en_US
dc.subject antiproliferative activity en_US
dc.subject Gene Expression Profiling en_US
dc.subject cell death en_US
dc.subject interleukin 17 en_US
dc.subject Antineoplastic Agents en_US
dc.subject Spinal Cord Diseases en_US
dc.subject lymphocyte proliferation en_US
dc.subject alpha2a interferon en_US
dc.subject Ascorbic Acid en_US
dc.subject Cell Death en_US
dc.subject DNA synthesis en_US
dc.subject gene control en_US
dc.subject Immunologic Factors en_US
dc.subject Interferon-alpha en_US
dc.subject Leukemia-Lymphoma, Adult T-Cell en_US
dc.subject Microarray Analysis en_US
dc.subject microRNA 155 en_US
dc.subject Organ Culture Techniques en_US
dc.subject Th17 cell en_US
dc.title Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1371/journal.pntd.0001729
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.06
dc.relation.issn 1935-2735


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