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Pharmacoepidemiologic studies suggest that statins may improve lower limb arthroplasty survival, potentially through pleiotropic anti-inflammatory effects, but the biology underpinning this remains unclear. The aim of this study was to investigate the effect of simvastatin on orthopaedic bio-material-induced inflammation in-vitro. Gene expression was measured by qPCR and protein secretion was measured by ELISA and Meso scale discovery assays. In THP-1 macrophages, co-culture with simvastatin significantly abrogated cobalt-mediated increases in\n                    <jats:italic>IL-8<\/jats:italic>\n                    gene expression in addition to IL-8, IL-1\u03b2, CCL3, CCL4 and CCL20 protein secretion. Simvastatin also inhibited zirconium oxide-mediated levels of CCL2 and CCL4, as well as alumina oxide-mediated increases in CCL2. These novel findings demonstrate that statins can significantly reduce orthopaedic biomaterial-induced expression of pro-inflammatory cytokines in-vitro. As statins are widely used in clinical practice and inexpensive, this provides an exciting basis for future work to leverage statins to reduce the impact of a burgeoning demand for revision arthroplasty on patients.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-56507-4","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T11:05:51Z","timestamp":1782558351000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The effect of simvastatin on orthopaedic biomaterial induced inflammation"],"prefix":"10.1038","volume":"16","author":[{"given":"Sami A.","family":"Anjum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Jamieson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Deehan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Kirby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Tyson-Capper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"56507_CR1","unstructured":"National Joint Registry for England. 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