Aseptic Loosening Of Total Hip Replacement Research Articles

The role of the TH1 and TH2 immune responses in loosening and osteolysis of cemented total hip replacements.

The mechanisms underlying the development of osteolysis and aseptic loosening have an impact on the longevity of total hip replacements (THRs). This study examines the specific roles of lymphocytes in the TH1 and TH2 subsets in osteolysis and aseptic loosening of THR. Tissue from periprosthetic regions from patients with loose, cemented acetabular components were used to determine the TH1 and TH2 cytokine profile. Twelve tissue specimens from patients with radiographic signs of osteolysis, and nine tissue specimens from patients with no signs of osteolysis were harvested during revision surgery. Immunohistochemistry using primary antibodies against CD3, interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 was performed on frozen sections to determine the percentage of positive cells for each of the sections. No statistically significant differences in the percentage of positive cells expressing cytokines characteristic of the TH1 pathway (IFN-gamma, IL-2) or TH2 pathway (IL-4, IL-10) were found when comparing osteolytic and non-osteolytic tissues. However, significant numbers of T cells (averaging about 10% of the total cells) and TH1 and TH2 immune cytokines (averaging 3-5% of cells) implicate a possible role for immune processes at the prosthetic interface.

No lymphokines in T-cells around loosened hip prostheses.

Research results have been contradictory about the role of lymphocytes and immune response in aseptic loosening of total hip replacement (THR). Conclusive evidence is still lacking in spite of extensive in vivo and in vitro studies. Our study was designed to check whether T-cells were activated and if they produced lymphokines in synovial membrane-like interface tissue around loosened THRs. Tissue sections were stabilized and permeabilized to allow the cytokine-specific antibodies to penetrate through the cell membrane and the membranes of intracellular organelles. This technique, combined with computer-assisted image analysis, permits the detection and quantitation of lymphokine-producing cells. We found that the number of T-cells was low, and none of the T-cells was activated, as shown by the absence of interleukin-2 receptor (IL-2R) immunoreactivity. There was no cell producing lymphokines, such as interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and tumor necrosis factor-beta (TNF-beta). Our results suggest that T-cell-mediated immune response is not actively involved in aseptic loosening of THR.

Increased expression of EMMPRIN in the tissue around loosened hip prostheses.

Matrix metalloproteinases (MMPs) have been shown to play a role in aseptic loosening of total hip replacement (THR). Extracellular matrix metalloproteinase inducer (EMMPRIN) can upregulate expression of several MMPs but has little effect on their tissue inhibitor (TIMP). Using the avidin-biotin-peroxidase complex immunostaining method, we detected strong immunoreactivity of EMMPRIN in the lining-like layers, sublining area and vascular endothelium of synovial membrane-like interface tissue around loosened prostheses. In contrast, EMMPRIN staining was very weak in the synovial samples from patients with hip arthrosis. Double immunofluorescence labeling revealed EMMPRIN/MMP-1 double-positive cells in lining-like layers and the sublining area of interface tissue. Our findings indicate that EMMPRIN expression is upregulated in interface tissue, and that locally accumulated EMMPRIN may modulate MMP-1 expression. An imbalance in the activity of MMPs and TIMP may lead to tissue destruction and periprosthetic osteolysis. These biological responses, combined with mechanical stress caused by micromotion and oscillating fluid pressure, may eventually cause aseptic loosening of THR.

Interleukin-11 (IL-11) in Aseptic Loosening of Total Hip Replacement (THR)

The chronic inflammatory response to abrasion particles from total hip replacement (THR) is believed to cause osteolysis and to contribute to prosthetic loosening. The expression of interleukin-11(IL-11) and its major cellular sources in the interface and pseudocapsular tissues obtained from total hip revisions performed for aseptic loosening were investigated. The avidin-biotin-peroxidase complex (ABC) and alkaline phosphatase-anti-alkaline phosphatase (APAAP) methods were used for staining and VIDAS image analysis for quantification. IL-11 was found in the interface and pseudocapsular tissues in the aseptic loosening of THR. IL-11 containing cells were more numerous in the interface (760 +/- 171 cells) and pseudocapsular tissues (684 +/- 171 cells) than in the control synovial tissue (235 +/- 68 cells). Because IL-11 is an important component of cytokine network mediating osteoblast-osteoclast communication in normal and pathological bone remodeling, the current findings suggest that IL-11 may contribute to periprosthetic osteolysis and to the loosening of THR.