The effect of simvastatin on orthopaedic biomaterial induced inflammation.

The most common indications for lower limb revision arthroplasty are aseptic loosening of the implant and adverse reactions to particulate debris, both of which are driven by host immune responses to orthopaedic biomaterials. 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 IL-8 gene expression in addition to IL-8, IL-1β, 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.