Methotrexate an Old Drug with New Tricks.
Adenosine
Alarmins
Anti-Inflammatory Agents
/ pharmacology
Antirheumatic Agents
/ pharmacology
Arthritis
/ drug therapy
Arthritis, Rheumatoid
/ drug therapy
Cytokines
/ metabolism
Folic Acid
HMGB1 Protein
/ drug effects
Humans
Immunity, Innate
Inflammation
Matrix Metalloproteinases
/ drug effects
Methotrexate
/ immunology
NF-kappa B
/ drug effects
Polyamines
Prostaglandins
Reactive Oxygen Species
alarmin
arthritis
chikungunya
inflammation
innate immunity
methotrexate
pharmacology
rheumatoid arthritis
virus
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
10 Oct 2019
10 Oct 2019
Historique:
received:
23
07
2019
revised:
16
09
2019
accepted:
30
09
2019
entrez:
30
10
2019
pubmed:
30
10
2019
medline:
1
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31658782
pii: ijms20205023
doi: 10.3390/ijms20205023
pmc: PMC6834162
pii:
doi:
Substances chimiques
Alarmins
0
Anti-Inflammatory Agents
0
Antirheumatic Agents
0
Cytokines
0
HMGB1 Protein
0
NF-kappa B
0
Polyamines
0
Prostaglandins
0
Reactive Oxygen Species
0
Folic Acid
935E97BOY8
Matrix Metalloproteinases
EC 3.4.24.-
Adenosine
K72T3FS567
Methotrexate
YL5FZ2Y5U1
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
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