{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T12:55:07Z","timestamp":1782219307510,"version":"3.54.5"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Rheumatoid arthritis is associated with excess cardiovascular morbidity and mortality despite the frequent presence of relatively low circulating lipid levels during active disease, a phenomenon commonly described as the lipid paradox. Interleukin-6 is central to this paradox because it links synovial inflammation with hepatic acute-phase responses, lipoprotein remodeling, thromboinflammatory pathways, and vascular injury. In this narrative review, we examine how IL-6 blockade reshapes the interpretation of lipid changes in rheumatoid arthritis and whether post-treatment cholesterol elevation should be viewed as isolated metabolic harm or as part of a broader process of hepatic inflammatory-lipoprotein remodeling. Mechanistic and translational evidence suggests, but does not yet prove, that active rheumatoid arthritis is characterized not only by reduced lipid concentrations, but also by dysfunctional high-density lipoprotein, oxidative lipoprotein modification, increased serum amyloid A loading, and vascular inflammation. After IL-6 pathway inhibition, particularly with tocilizumab and sarilumab, total cholesterol and low-density lipoprotein cholesterol often increase early; however, these changes may occur alongside reductions in C-reactive protein, serum amyloid A, lipoprotein(a), fibrinogen, and D-dimers, as well as selected improvements in lipoprotein function. Current hard cardiovascular outcome data generally support cardiovascular neutrality rather than a clear increase in major adverse cardiovascular events, although uncertainty remains for specific outcomes, vascular territories, and patient subgroups. Overall, lipid elevation after IL-6 blockade should prompt contextual cardiovascular risk refinement rather than reflexive interpretation as isolated cholesterol-mediated harm.<\/jats:p>","DOI":"10.3389\/fcvm.2026.1847053","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T12:34:50Z","timestamp":1782218090000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid changes after interleukin-6 blockade in rheumatoid arthritis: beyond cholesterol elevation toward hepatic inflammatory-lipoprotein remodeling"],"prefix":"10.3389","volume":"13","author":[{"given":"Na","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Rheumatology, The Affiliated Hospital to Changchun University of Chinese Medicine","place":["Changchun, 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