ArticleEULAR rheumatology open2026
4-Octyl itaconate inhibits synovial fibroblast activation by targeting Nrf2 to exert anti-inflammatory effects in rheumatoid arthritis.
Article in EULAR rheumatology open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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13 authors.
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Abstract
Objectives: Fibroblast-like synoviocytes (FLS) are pivotal for the expansive growth and invasiveness of rheumatoid synovitis, and patients with a fibroblastic-rich pathotype respond poorly to currently approved antirheumatic drugs. The aim of this project was to examine the anti-inflammatory effects of the nuclear factor erythroid 2-related factor 2 (Nrf2) activator 4-octyl itaconate (4-OI) on inflammatory rheumatoid arthritis (RA)-FLS-dominated pathology. Methods: Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and autologous cocultures of RA-FLS and peripheral blood mononuclear cells were cultured with 4-OI, corticosteroids or antitumor necrosis factor alpha antibodies and analysed for inflammatory activity with Western blot and enzyme-linked immunosorbent assay. 4-OI-induced transcription factor Nrf2 was genetically ablated in immortalised FLS using Clustered Regurlarly Interspaced Short Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) gene editing. Results: In RA-FLS in both monocultures and autolog cocultures, 4-OI treatment mediated an increase in gene expression of the Nrf2-regulated protein heme oxygenase-1 and NAD(P)H quinone dehydrogenase 1 with a concomitant decrease in monocyte chemoattractant protein-1 and specifically in monocultures also of interleukin 6 secretion. Silencing of Nrf2 reduced the effect mediated by 4-OI in RA-FLS. In the methylated bovine serum albumin mouse model, local administration of 4-OI significantly reduced joint swelling. In the collagen-induced arthritis model, a similar trend was seen accompanied by a significant reduction of interleukin 6 in serum. Conclusions: 4-OI ameliorates inflammation in models of RA, particularly in FLS-driven disease pathology. Overall, human
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