Cellular profile and cytokine production at prosthetic interfaces: Study of tissues retrieved from revised hip and knee replacements

Abstract

The tissues surrounding 65 cemented and 36 cementless total joint replacements undergoing revision were characterised for cell types by immunohistochemistry and for cytokine expression by in situ hybridisation. We identified three distinct groups of revised implants: loose implants with ballooning radiological osteolysis, loose implants without osteolysis, and well-fixed implants. In the cemented series, osteolysis was associated with increased numbers of macrophages (p = 0.0006), T-lymphocyte subgroups (p = 0.03) and IL-1 (p = 0.02) and IL-6 (p = 0.0001) expression, and in the cementless series with increased numbers of T-lymphocyte subgroups (p = 0.005) and increased TNF alpha expression (p = 0.04). For cemented implants, the histological, histochemical and cytokine profiles of the interface correlated with the clinical and radiological grade of loosening and osteolysis. Our findings suggest that there are different biological mechanisms of loosening and osteolysis for cemented and cementless implants. T-lymphocyte modulation of macrophage function may be an important interaction at prosthetic interfaces.

Peri-prosthetic tissue cells show osteogenic capacity to differentiate into the osteoblastic lineage

“…Since there is no suitable tissue to serve as a control for peri‐prosthetic tissue, we used different control cell lines to determine the relative expression. A high‐variation in the gene expression levels between donors was observed, indicating heterogeneous populations of cells, which is in line with several studies evaluating the cellular content of peri‐prosthetic tissue 43, 44, 45. Although we did not find an association between the responsiveness to osteogenic stimuli and the cell content, it is not excluded that the high‐inter‐donor variability in gene expression levels might account for the high‐inter‐donor variability in response to osteogenic stimuli.…”

Do Tissues From THA Revision of Highly Crosslinked UHMWPE Liners Contain Wear Debris and Associated Inflammation?

“…Although animal models have shown T cells are dispensable in the development of osteolysis [25,39,72], a recent in vitro study showed depletion of T cells or the addition of RANK-Fc to human peripheral blood cell cultures equally reduced osteoclast formation in response to RANKL [65]. Additionally, the current findings and those of others [28,61] support the potential involvement of T cells in human osteolytic responses after recruitment by chemotactic factors released from activated macrophages [5,19,63,68]. In agreement with other reports, we observed distinct regional and patient differences in the immune cell responses [8,28,36,40] and notably a corresponding heterogeneity in UHMWPE particle number.…”

“…However, in these studies, there was no attempt to correlate the presence of wear debris with immune cells, to separately evaluate the presence of macrophages and histiocytes using a size exclusion cutoff, or to determine macrophage and T cell number in the entire tissue section. Macrophages, unlike debris-laden histiocytes, have the potential to upregulate proinflammatory cytokine expression [49], and only by determining the number of these cells in each section can their involvement be assessed given the known intratissue variability [8,28,36,40]. In our study [8] and others [28,68], T cells were observed near blood vessels and in pseudocapsular and periprosthetic tissues associated with macrophages.…”

“…In general, the colocalization of wear debris and macrophages/histiocytes is well-established [28,41], and several studies have identified the presence of T cells in periprosthetic tissues, with the incidence ranging from categorically absent to 30% [28,40,41]. However, in these studies, there was no attempt to correlate the presence of wear debris with immune cells, to separately evaluate the presence of macrophages and histiocytes using a size exclusion cutoff, or to determine macrophage and T cell number in the entire tissue section.…”

“…Although the role of T cells in aseptic loosening is controversial, a recent study has identified a functionally active subset of T C cells capable of downregulating T H cells [65], which may explain the inconsistent detection of lymphokines in tissues around loosened prostheses [45,65]. Additional studies showing correlations between increased numbers of T H and T C cells and radiographic osteolysis [28,61] further implicate T cell involvement in bone remodeling. However, others only attribute a substantial involvement of T cells in the inflammatory Type IV hypersensitivity response to metal particles and/or ions [13,48,60,76].…”