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Titanium (Ti) forms aggregates with serum proteins, which activate and cause release of the cytokine interleukin (IL\u20101\u03b2) from human macrophages. It was hypothesized that cobalt (Co) ions can interact in the formation of pro\u2010inflammatory aggregates, formed by titanium. To test this hypothesis, we differentiated THP\u20101 cells into macrophages and exposed them to Ti ions alone or in combination with Co ions to investigate if IL\u20101\u03b2 release and cytotoxicity were affected. We also investigated aggregate formation, cell uptake and human biopsies with inductively coupled plasma atomic emission spectroscopy and electron microscopy. Co at a concentration of 100 \u00b5M neutralized the IL\u20101\u03b2 release from human macrophages and affected the aggregate formation. The aggregates formed by Ti could be detected in the cytosol of macrophages. In the presence of Co, the Ti\u2010induced aggregates were located in the cytosol of the cultured macrophages, but outside the lysosomal structures. It is concluded that Co can neutralize the Ti\u2010induced activation and release of active IL\u20101\u03b2 from human macrophages<jats:italic>in vitro<\/jats:italic>. Also, serum proteins are needed for the formation of metal\u2010protein aggregates in cell medium. Furthermore, the structures of the aggregates as well as the localisation after cellular uptake differ if Co is present in a Ti solution. Phagocytized aggregates with a similar appearance seen<jats:italic>in vitro<\/jats:italic>with Ti present, were also visible in a sample from human peri\u2010implant tissue. \u00a9 2018 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2518\u20132530, 2018.<\/jats:p>","DOI":"10.1002\/jbm.a.36447","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T15:31:22Z","timestamp":1525102282000},"page":"2518-2530","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effect of cobalt ions on the interaction between macrophages and titanium"],"prefix":"10.1002","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5992-8135","authenticated-orcid":false,"given":"Mattias","family":"Pettersson","sequence":"first","affiliation":[{"name":"Prosthetic Dentistry, Ume\u00e5 University Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4764-1246","authenticated-orcid":false,"given":"Jean","family":"Pettersson","sequence":"additional","affiliation":[{"name":"Analytic Chemistry, BMC, Department of Chemistry Uppsala University 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