ArticlePLoS neglected tropical diseases2018
Immunomodulatory drug methotrexate used to treat patients with chronic inflammatory rheumatisms post-chikungunya does not impair the synovial antiviral and bone repair responses.
Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Pathogens in rheumatoid arthritis: epidemiological, mechanistic, and clinical insights.Biomarker research · 2026Review
- Immunopathological mechanisms and targeted intervention strategies for chronic chikungunya arthritis: from viral persistence to autoimmunity.Frontiers in immunology · 2026Review
- Chronic Diseases and Influenza Vaccines.Vaccines · 2025Review
- Therapy for Chikungunya Arthritis: A Study of 133 Brazilian Patients.The American journal of tropical medicine and hygiene · 2023Article
- Review
- Anti-Alphaviral Alkaloids: Focus on Some Isoquinolines, Indoles and Quinolizidines.Molecules (Basel, Switzerland) · 2022Review
- Development and Application of Treatment for Chikungunya Fever.Research and reports in tropical medicine · 2022Review
- Article
- Quercetin can reduce viral RNA level of O'nyong-nyong virus and resulting innate immune cytokine responses in cultured human synovial fibroblasts.Scientific reports · 2021Article
- Robust COX-2-mediated prostaglandin response may drive arthralgia and bone destruction in patients with chronic inflammation post-chikungunya.PLoS neglected tropical diseases · 2021Article
- Overview on Chikungunya Virus Infection: From Epidemiology to State-of-the-Art Experimental Models.Frontiers in microbiology · 2021Review
- Evaluation of mechanisms of action of re-purposed drugs for treatment of COVID-19.Cellular immunology · 2020Review
- Chronic Chikungunya Arthritis and Rheumatoid Arthritis: What They Have in Common.The American journal of medicine · 2020Review
- Methotrexate an Old Drug with New Tricks.International journal of molecular sciences · 2019Review
- Rheumatic manifestations of chikungunya: emerging concepts and interventions.Nature reviews. Rheumatology · 2019Review
- The Clinical Features, Pathogenesis and Methotrexate Therapy of Chronic Chikungunya Arthritis.Viruses · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chikungunya virus (CHIKV) is a mosquito-transmitted RNA alphavirus causing major outbreaks of infectious chronic inflammatory rheumatisms (CIR). Recently, methotrexate (MTX), a disease modifying anti-rheumatic drug has been used successfully to treat patients suffering from rheumatoid-like arthritis post-CHIK but its immunomodulatory activity in the context of viral persistence has been a matter of concerns. We herein used a model of primary human synovial fibroblasts (HSF) and the synthetic molecule polyriboinosinic:polyribocytidylic acid (PIC) to mimic chronic infectious settings in the joints of CHIKV infected patients. The innate antiviral immune and inflammatory responses were investigated in response to MTX used at the therapeutic concentration of 1 μM. We found that MTX did not affect cellular viability as indicated by the LDH release assay. By quantitative RT-PCR, we observed that HSF responded robustly to PIC by increasing ISG15 and IFNβ mRNA levels. Furthermore, PIC upregulated the mRNA expression of two of the major pattern recognition receptors, RIG-I and MDA5 involved in the innate immune detection of viral RNA. MTX did not impact the antiviral response of PIC on ISG15, IFNβ, RIG-I and MDA5 mRNA expressions. MTX alone or combined with PIC did not affect the expression of proinflammatory CCL2 and CXCL8 chemokines. PIC strongly upregulated the mRNA and protein expression of osteoclastogenic factors (IL-6, GM-CSF but not RANKL). Critically, MTX treatment alone or combined with PIC did not affect the expression of all three tested osteoclastogenic cytokines. We found that MTX alone did not increase the capacity of CHIKV to infect and replicate in HSF. In conclusion, our study argues for a beneficial effect of MTX to treat CIR post-CHIKV given that it does not critically impact the antiviral, the proinflammatory and the bone tissue remodeling responses of synovial cells.
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