Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy.
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) m...
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Online Access: | https://doi.org/10.1371/journal.pntd.0001729 https://doaj.org/article/1a3b81d0d710463db6870f3c5b790754 |
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ftdoajarticles:oai:doaj.org/article:1a3b81d0d710463db6870f3c5b790754 2023-05-15T15:14:17+02:00 Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. Britta Moens Daniele Decanine Soraya Maria Menezes Ricardo Khouri Gilvanéia Silva-Santos Giovanni Lopez Carolina Alvarez Michael Talledo Eduardo Gotuzzo Ramon de Almeida Kruschewsky Bernardo Galvão-Castro Anne-Mieke Vandamme Johan Van Weyenbergh 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001729 https://doaj.org/article/1a3b81d0d710463db6870f3c5b790754 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3404116?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0001729 https://doaj.org/article/1a3b81d0d710463db6870f3c5b790754 PLoS Neglected Tropical Diseases, Vol 6, Iss 7, p e1729 (2012) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2012 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001729 2022-12-31T08:13:46Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 6 7 e1729 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Britta Moens Daniele Decanine Soraya Maria Menezes Ricardo Khouri Gilvanéia Silva-Santos Giovanni Lopez Carolina Alvarez Michael Talledo Eduardo Gotuzzo Ramon de Almeida Kruschewsky Bernardo Galvão-Castro Anne-Mieke Vandamme Johan Van Weyenbergh Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Britta Moens Daniele Decanine Soraya Maria Menezes Ricardo Khouri Gilvanéia Silva-Santos Giovanni Lopez Carolina Alvarez Michael Talledo Eduardo Gotuzzo Ramon de Almeida Kruschewsky Bernardo Galvão-Castro Anne-Mieke Vandamme Johan Van Weyenbergh |
author_facet |
Britta Moens Daniele Decanine Soraya Maria Menezes Ricardo Khouri Gilvanéia Silva-Santos Giovanni Lopez Carolina Alvarez Michael Talledo Eduardo Gotuzzo Ramon de Almeida Kruschewsky Bernardo Galvão-Castro Anne-Mieke Vandamme Johan Van Weyenbergh |
author_sort |
Britta Moens |
title |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
title_short |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
title_full |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
title_fullStr |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
title_full_unstemmed |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
title_sort |
ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over ifn-α in htlv-1-associated myelopathy. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pntd.0001729 https://doaj.org/article/1a3b81d0d710463db6870f3c5b790754 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 6, Iss 7, p e1729 (2012) |
op_relation |
http://europepmc.org/articles/PMC3404116?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0001729 https://doaj.org/article/1a3b81d0d710463db6870f3c5b790754 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001729 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
6 |
container_issue |
7 |
container_start_page |
e1729 |
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1766344747255857152 |