ArticleRheumatology (Oxford, England)2021
The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis.
Article in Rheumatology (Oxford, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Systematic review and meta-analysis of cardiovascular associated biomarkers in adults with asymptomatic autoimmune diseases.Frontiers in cardiovascular medicine · 2025Pooled it
- Accelerated atherosclerosis in rheumatoid arthritis: a systematic review.F1000Research · 2022Pooled it
- Selective inhibition of IL-6 trans-signalling reveals distinct mechanisms of human classic and trans-signalling receptor-complex formation.Communications biology · 2026Article
- Prompt clinical and electrophysiological remission of refractory peripheral neuropathy in long-standing rheumatoid arthritis with tocilizumab: a case report.Frontiers in immunology · 2026Article
- From Joints to the Heart: An Integrated Perspective on Systemic Inflammation.Life (Basel, Switzerland) · 2025Review
- Cardiometabolic Risk in Psoriatic Arthritis: A Hidden Burden of Inflammation and Metabolic Dysregulation.Metabolites · 2025Review
- Interleukin-6: Cardiovascular Aspects of Long-Term Cytokine Suppression in Patients with Rheumatoid Arthritis.International journal of molecular sciences · 2024Article
- Interleukin-6 positively correlates with cardiovascular disease predictor algorithms and biomarker in rheumatoid arthritis patients.Journal of cellular and molecular medicine · 2024Article
- Shared inflammatory pathways of rheumatoid arthritis and atherosclerotic cardiovascular disease.Nature reviews. Rheumatology · 2023Review
- Integrative Mendelian randomization reveals the soluble receptor for advanced glycation end products as protective in relation to rheumatoid arthritis.Scientific reports · 2023Article
- Tracking Cardiovascular Comorbidity in Models of Chronic Inflammatory Disease.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Systemic complications of rheumatoid arthritis: Focus on pathogenesis and treatment.Frontiers in immunology · 2022Review
- Non-pharmacological treatment in difficult-to-treat rheumatoid arthritis.Frontiers in medicine · 2022Review
- Treatment of Cardiovascular Disease in Rheumatoid Arthritis: A Complex Challenge with Increased Atherosclerotic Risk.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Soluble IL-6R-mediated IL-6 trans-signaling activation contributes to the pathological development of psoriasis.Journal of molecular medicine (Berlin, Germany) · 2021Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesCardiovascular (CV) mortality in RA patients is 50% higher than in the general population. There is increasing recognition that systemic inflammation is a major driver of this. IL-6 is implicated in cardiovascular disease (CVD) in the general population but its role in CVD in RA is undefined. Of the two modes of IL-6 signalling, trans-signalling is pro-inflammatory whereas classical signalling is linked with inflammation resolution. This study examines the role of IL-6 trans-signalling in CVD in a mouse model and patients with RA.
methodsMyography determined the effect of IL-6 trans-signalling blockade, using sgp130Fc, on aortic constriction in murine collagen-induced arthritis. Serum CCL2 and sVCAM-1 as soluble biomarkers of sIL-6R trans-signalling were investigated in a human cross-sectional study. An observational longitudinal study investigated the association between these biomarkers and progression of subclinical atherosclerosis in early RA by measuring carotid intima-media thickness (CIMT).
resultssgp130Fc reduced arthritis severity, serum CCL2 and sVCAM-1 and restored vascular function in collagen-induced arthritis (CIA). In established RA, sVCAM-1 correlated with the 28-joint DAS (DAS28) and CV risk. In early RA, baseline DAS28 was associated with CIMT change at 6 months. CIMT 'rapid progressors' at 12 months had higher baseline sVCAM-1, haemoglobin A1c, cholesterol:high-density lipoprotein cholesterol ratio and LDL cholesterol.
conclusionsIL-6 trans-signalling plays a pivotal role in vascular dysfunction in CIA. In early RA, sVCAM-1 was associated with progression of subclinical atherosclerosis. Inflammation from RA onset in CVD-susceptible individuals may accelerate atherosclerosis. IL-6 trans-signalling blockade may be beneficial to RA patients and perhaps for atherosclerosis in the general population.
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