Assessment of the role of cytokines in bone resorption in patients with total joint replacement

Periprosthetic osteolysis is known to be a consequence of a local chronic inflammatory reaction in the synovial tissue and the bone-implant interface membrane, and is mediated by macrophages (M phi) and foreign body multinucleated giant cells (MNGC) in these tissues. Activated M phi produce major classes of cytokines which have been documented in the regulation of bone cell formation, function and activity. In rheumatoid arthritis, inflammatory mediators released by M phi participate significantly in articular tissue destruction. In this study we have analysed the production and tissue distribution of 4 cytokines in the interface membranes obtained from patients with osteolysis associated aseptic loosening and in rheumatoid synovium to determine their role in the functional transformation of effector cells in these two conditions. The production of IL-1, GM-CSF, IL-6 and TNF-alpha was assessed using immunohistochemistry on cryostat sections of the interface a nd the synovial tissues. IL-1 a nd GM-CSF were detected in significantly high numbers of the inflammatory M phi in both RA and aseptic loosening. A specific pattern of expression was noted in the interface. IL-1 production was sporadic throughout the sections, while GM-CSF was immunolocalized in a distinct subset of phagocytic macrophages on the implant side. IL-6 showed moderate expression in both conditions and was more widely produced at sites near the bone side in the interface. TNF-alpha expression was absent or reduced in the interface but was more abundant in RA synovial M phi. The differential expression of cytokines indicates that bone lysis in these two pathological conditions is mediated by different mechanisms and regulated by different cytokines.