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Modulation of macrophage polarization with interleukin\u20104 (IL\u20104) has emerged as an effective means to limit wear particle\u2010induced osteolysis. The aim of this study was to evaluate the efficacy of local IL\u20104 delivery in treating preexisting particle\u2010induced osteolysis. To this end, recently established 8\u00a0week modification of murine continuous femoral intramedullary particle infusion model was utilized. Subcutaneous infusion pumps were used to deliver polyethylene (PE) particles into mouse distal femur for 4\u2009weeks to induce osteolysis. IL\u20104 was then added to the particle infusion for another 4\u2009weeks. This delayed IL\u20104 treatment (IL\u20104 Del) was compared to IL\u20104 delivered continuously (IL\u20104 Cont) with PE particles from the beginning and to the infusion of particles alone for 8\u2009weeks. Both IL\u20104 treatments were highly effective in preventing and repairing preexisting particle\u2010induced bone loss as assessed by \u03bcCT. Immunofluorescence indicated a significant reduction in the number of F4\/80\u2009+\u2009iNOS\u2009+\u2009M1 macrophages and increase in the number of F4\/80\u2009+\u2009CD206\u2009+\u2009M2 macrophages with both IL\u20104 treatments. Reduction in the number of tartrate resistant acid phosphatase + osteoclasts and increase in the amount of alkaline phosphatase (ALP) + osteoblasts was also observed with both IL\u20104 treatments likely explaining the regeneration of bone in these samples. Interesting, slightly more bone formation and ALP + osteoblasts were seen in the IL\u20104 Del group than in the IL\u20104 Cont group although these differences were not statistically significant. The study is a proof of principle that osteolytic lesions can be repaired via modulation of macrophage polarization.<\/jats:p>","DOI":"10.1002\/jbm.a.37142","type":"journal-article","created":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T12:34:53Z","timestamp":1608381293000},"page":"1512-1520","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Interleukin\u20104 repairs wear particle induced osteolysis by modulating macrophage polarization and bone turnover"],"prefix":"10.1002","volume":"109","author":[{"given":"Jukka","family":"Pajarinen","sequence":"first","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery Stanford University School of Medicine  Stanford California USA"},{"name":"Department of Musculoskeletal and Plastic Surgery University of Helsinki and Helsinki University Hospital  Helsinki Finland"},{"name":"Department of Medicine, Clinicum University of Helsinki 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