ArticleArthritis research & therapy2005
The active metabolite of leflunomide, A77 1726, interferes with dendritic cell function.
Article in Arthritis research & therapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- Preliminary evaluation in rheumatoid arthritis activity in patients treated with TNF-alpha blocker plus methotrexate versus methotrexate or leflunomide alone.Rheumatology international · 2007Trial
- Study on the Mechanism of the Combination of Methotrexate and Leflunomide in the Treatment of Rheumatoid Arthritis Based on Network Pharmacology, Molecular Docking, andCombinatorial chemistry & high throughput screening · 2025Article
- Effectiveness of methotrexate and leflunomide as corticoid-sparing drugs in patients with polymyalgia rheumatica.Rheumatology advances in practice · 2024Article
- Regulation of Myeloid Dendritic Cells by Synthetic and Natural Compounds for the Treatment of Rheumatoid Arthritis.International journal of molecular sciences · 2022Review
- Impact of disease-modifying therapy on dendritic cells and exploring their immunotherapeutic potential in multiple sclerosis.Journal of neuroinflammation · 2022Review
- Development and Evaluation of Novel Leflunomide SPION Bioemulsomes for the Intra-Articular Treatment of Arthritis.Pharmaceutics · 2022Article
- Performance of leflunomide as a steroid-sparing agent in giant cell arteritis: A single-center, open-label study.Frontiers in medicine · 2022Article
- Suppression of Dendritic Cell Maturation by Kefir Peptides Alleviates Collagen-Induced Arthritis in Mice.Frontiers in pharmacology · 2021Article
- Toward Overcoming Treatment Failure in Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Mesenchymal stem cell therapy induces FLT3L and CD1cNature communications · 2019Article
- Does leflunomide have a role in giant cell arteritis? An open-label study.Clinical rheumatology · 2019Observational
- Dextromethorphan inhibits activations and functions in dendritic cells.Clinical & developmental immunology · 2013Article
- Leflunomide as a corticosteroid-sparing agent in giant cell arteritis and polymyalgia rheumatica: a case series.BioMed research international · 2013Article
- Prostaglandin D(2) in inflammatory arthritis and its relation with synovial fluid dendritic cells.Mediators of inflammation · 2013Article
- Immunosuppressive effects and mechanisms of leflunomide in dengue virus infection of human dendritic cells.Journal of clinical immunology · 2011Article
- Suppressed wound healing in a patient with rheumatoid arthritis taking leflunomide (arava).The Permanente journal · 2011Article
- Efficacy of leflunomide for treatment of immune-mediated polyarthritis in dogs: 14 cases (2006-2008).Journal of the American Veterinary Medical Association · 2010Article
- Maturation of dendritic cells depends on proteolytic cleavage by cathepsin X.Journal of leukocyte biology · 2008Article
- The active metabolite of leflunomide A771726 inhibits corneal neovascularization.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2008Article
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10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leflunomide, a potent disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis (RA), exhibits anti-inflammatory, antiproliferative and immunosuppressive effects. Although most of the beneficial effects of leflunomide have been attributed to its antimetabolite activity, mainly in T cells, other targets accounting for its potency might still exist. Because of mounting evidence for a prominent role of dendritic cells (DCs) in the initiation and maintenance of the immune response in RA, we analyzed the effect of the active metabolite of leflunomide (A77 1726; LEF-M) on phenotype and function of human myleloid DCs at several stages in their life cycle. Importantly, DCs differentiated in the presence of LEF-M exhibited an altered phenotype, with largely reduced surface expression of the critical co-stimulatory molecules CD40 and CD80. Furthermore, treatment of DCs during the differentiation or maturation phase with LEF-M aborted successful DC maturation. Exogenous addition of uridine revealed that DC modulation by LEF-M was independent of its proposed ability as an antimetabolite. In addition, the ability of DCs to initiate T-cell proliferation and to produce the proinflammatory cytokines IL-12 and tumour necrosis factor-alpha was markedly impaired by LEF-M treatment. As a molecular mechanism, transactivation of nuclear factor-kappaB, an transcription factor essential for proper DC function, was completely suppressed in DCs treated with LEF-M. These data indicate that interference with several aspects of DC function could significantly contribute to the beneficial effects of leflunomide in inflammatory diseases, including RA.
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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.