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Open AccessReview

Methotrexate an Old Drug with New Tricks

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Unité Mixte de Recherche Processus Infectieux en Milieu Insulaire Tropical (PIMIT), INSERM U1187, CNRS 9192, IRD 249, Université de La Réunion—Plateforme Technologique CYROI—2, rue Maxime Rivière, 97490 Sainte-Clotilde, France
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Service de Rhumatologie, CHU La Réunion site Félix Guyon, Allée des Topazes, CS11021, 97400 Saint Denis de La Réunion, France
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Laboratoire de biologie, CNR associé des arbovirus, CHU La Réunion site Félix Guyon, Allée des Topazes, CS11021, 97400 Saint Denis de La Réunion, France
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Service de Rhumatologie—Médecine Interne, CHU Morafeno, Route d’Ivoloina 501, Toamasina, Madagascar
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Pôle de Biologie, secteur Laboratoire d’Immunologie Clinique et Expérimentale de la zone de l’Océan Indien (LICE-OI), CHU La Réunion site Félix Guyon, Allée des Topazes, CS11021, 97400 Saint Denis de La Réunion, France
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 5023; https://doi.org/10.3390/ijms20205023
Received: 23 July 2019 / Revised: 16 September 2019 / Accepted: 30 September 2019 / Published: 10 October 2019
(This article belongs to the Section Molecular Immunology)
Methotrexate (MTX) is the first line drug for the treatment of a number of rheumatic and non-rheumatic disorders. It is currently used as an anchor disease, modifying anti-rheumatic drug in the treatment of rheumatoid arthritis (RA). Despite the development of numerous new targeted therapies, MTX remains the backbone of RA therapy due to its potent efficacy and tolerability. There has been also a growing interest in the use of MTX in the treatment of chronic viral mediated arthritis. Many viruses—including old world alphaviruses, Parvovirus B19, hepatitis B/C virus, and human immunodeficiency virus—have been associated with arthritogenic diseases and reminiscent of RA. MTX may provide benefits although with the potential risk of attenuating patients’ immune surveillance capacities. In this review, we describe the emerging mechanisms of action of MTX as an anti-inflammatory drug and complementing its well-established immunomodulatory activity. The mechanisms involve adenosine signaling modulation, alteration of cytokine networks, generation of reactive oxygen species and HMGB1 alarmin suppression. We also provide a comprehensive understanding of the mechanisms of MTX toxic effects. Lastly, we discussed the efficacy, as well as the safety, of MTX used in the management of viral-related rheumatic syndromes. View Full-Text
Keywords: methotrexate; arthritis; inflammation; alarmin; virus; chikungunya; rheumatoid arthritis; innate immunity; pharmacology methotrexate; arthritis; inflammation; alarmin; virus; chikungunya; rheumatoid arthritis; innate immunity; pharmacology
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Bedoui, Y.; Guillot, X.; Sélambarom, J.; Guiraud, P.; Giry, C.; Jaffar-Bandjee, M.C.; Ralandison, S.; Gasque, P. Methotrexate an Old Drug with New Tricks. Int. J. Mol. Sci. 2019, 20, 5023.

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