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Infection accounts for approximately 1.5 per cent of joint loosening and when it occurs it is a cause of serious concern to the surgeon. The loosening of prosthetic joints in the absence of infection is by far the most common reason for revision surgery and is known as aseptic loosening. While this may be multifactorial in terms of causation, and non-biological factors may contribute significantly in a particular individual, a significant part is undoubtedly played by the generation of wear debris, mainly from the bearing surfaces of the joint, and the cellular reaction to this in the implant bed. Phagocytic cells (macrophages and multinucleated giant cells) are the ones that remove foreign material from the tissues, and the ways in which these cells function in the interface between implant and bone are described. Mediators produced locally include numerous cytokines, enzymes and integrins. There is evidence for interactions between macrophages and locally recruited lymphocytes, which may or may not give rise to an immunologically mediated process.<\/jats:p>\n                  <jats:p>Sensitization of individuals having metal implants in place has been shown by positive skin tests or blood lymphocyte transformation tests and in these cases has been accompanied by loosening and failure of the replacement joint. The question remains as to whether this process is also present in a proportion of individuals with aseptic loosening in the absence of clearly defined clinical evidence of sensitization.<\/jats:p>\n                  <jats:p>\n                    Numerous studies performed by the author's group and, latterly, by others suggest that the cellular reactions detected in the tissues in cases of aseptic loosening are indeed those of contact sensitization. There is good evidence to show that a type IV cell-mediated immune reaction is taking place, with T\n                    <jats:sub>H<\/jats:sub>\n                    1 cell involvement and active antigen presentation. The extent to which sensitization is present in individual cases of aseptic loosening remains a subject for further work and this needs all the sophisticated molecular methods now available to modern biology to be applied in appropriate prospective clinical studies coupled with experimental models\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Immunological processes may play a more important part in joint loosening than previously considered.\n                  <\/jats:p>","DOI":"10.1098\/rsif.2008.0142","type":"journal-article","created":{"date-parts":[[2008,7,22]],"date-time":"2008-07-22T21:03:35Z","timestamp":1216760615000},"page":"1263-1278","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":166,"title":["The combined role of wear particles, macrophages and lymphocytes in the loosening of total joint prostheses"],"prefix":"10.1098","volume":"5","author":[{"given":"Peter A","family":"Revell","sequence":"first","affiliation":[{"name":"Eastman Dental Institute, Division of Biomaterials and Tissue Engineering, University College LondonLondon WC1X 8LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2008,7,22]]},"reference":[{"key":"e_1_3_1_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/33.4.309"},{"key":"e_1_3_1_3_1","first-page":"319","article-title":"Pathology of the bone\u2013implant interfaces","volume":"9","author":"Al-Saffar N","year":"1999","journal-title":"J. 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