ArticleAnnals of the rheumatic diseases2009
Inhibition of tumour necrosis factor and IL-17 production by leflunomide involves the JAK/STAT pathway.
Article in Annals of the rheumatic diseases, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 63 citations in OpenAlex.
- The Role of Pharmacogenetics in the Effectiveness of Rheumatoid Arthritis Treatment with Leflunomide.Genes · 2026Review
- Integrative biochemical and computational analysis of leflunomide-induced redox alterations in Nauphoeta cinerea.Scientific reports · 2025Article
- Antirheumatic drug leflunomide attenuates atherosclerosis by regulating lipid metabolism and endothelial dysfunction via DHODH/AMPK signaling pathway.International journal of biological sciences · 2024Article
- Effectiveness of methotrexate and leflunomide as corticoid-sparing drugs in patients with polymyalgia rheumatica.Rheumatology advances in practice · 2024Article
- Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis.Pharmacology & therapeutics · 2023Review
- Tofacitinib combined with leflunomide for treatment of psoriatic arthritis with IgA nephropathy: a case report with literature review.Clinical rheumatology · 2022Review
- Plasma interleukin-23 and circulating IL-17AArthritis research & therapy · 2022Article
- Cell-Based Double-Screening Method to Identify a Reliable Candidate for Osteogenesis-Targeting Compounds.Biomedicines · 2022Article
- Review
- Teriflunomide provides protective properties after oxygen-glucose-deprivation in hippocampal and cerebellar slice cultures.Neural regeneration research · 2021Article
- The Mitochondria-Independent Cytotoxic Effect of Leflunomide on RPMI-8226 Multiple Myeloma Cell Line.Molecules (Basel, Switzerland) · 2021Article
- Candidate drug replacements for quinacrine in cutaneous lupus erythematosus.Lupus science & medicine · 2020Review
- Immunological Aspects of Approved MS Therapeutics.Frontiers in immunology · 2019Review
- From Leflunomide to Teriflunomide: Drug Development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis.Current neuropharmacology · 2017Review
- In vitro evaluation of physiologically relevant concentrations of teriflunomide on activation and proliferation of primary rodent microglia.Journal of neuroinflammation · 2016Article
- Biomarkers predicting a need for intensive treatment in patients with early arthritis.Current pharmaceutical design · 2015Review
- Molecular pharmacodynamics of new oral drugs used in the treatment of multiple sclerosis.Drug design, development and therapy · 2014Review
- Leflunomide: friend or foe for systemic lupus erythematosus?Rheumatology international · 2013Review
- An update of teriflunomide for treatment of multiple sclerosis.Therapeutics and clinical risk management · 2013Article
- Leflunomide as a corticosteroid-sparing agent in giant cell arteritis and polymyalgia rheumatica: a case series.BioMed research international · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo study the effects of different disease-modifying antirheumatic drugs (DMARD) on different events mediated by IL-15-activated lymphocytes.
methodsPeripheral blood lymphocytes (PBL) were isolated from healthy donors and activated with IL-15 after exposure to different DMARD: leflunomide, cyclosporin A, methotrexate, mycophenolic acid, FK-506, sulphasalazine and sodium aurothiomalate. The expression of different surface molecules on the PBL was then determined by flow cytometry. Cells were also co-cultured with the monocytic cell line THP-1 and the tumour necrosis factor (TNF) concentration in the supernatant was measured after 24 h using an immunoenzyme assay. The effect of the aforementioned drugs on IL-17 production by IL-15-activated PBL was also studied.
resultsTreatment of PBL with leflunomide, cyclosporin A and FK-506 inhibited the IL-15-induced expression of both CD54 and CD69 by PBL, as well as TNF production in co-cultures of activated PBL and THP-1 cells. The downregulation of CD54 and CD69 in PBL was correlated with the inhibition of TNF production. Likewise, leflunomide, cyclosporin A and FK-506 all inhibited IL-17 production in IL-15-activated PBL. Interestingly, the effect of leflunomide was not reverted by the presence of uridine in the medium. In addition, leflunomide inhibited the phosphorylation of STAT6 in vitro.
conclusionInhibition of the JAK/STAT pathway may represent an additional effect of leflunomide in chronic polyarthritis because it impairs certain events that control proinflammatory TNF and IL-17 cytokine production.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.