Assessing osteolysis with use of high-throughput protein chips.

BACKGROUND

Previous studies of bone resorption around failed joint replacements have focused on a limited number of cytokines, primarily tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, and IL-6, with use of enzyme-linked immunosorbent assay and immunohistochemistry techniques. In this study, we utilized high-throughput protein chips to profile twenty-nine inflammatory cytokines around failed total joint replacements.

METHODS

Peri-implant granulomatous tissues were harvested from around the failed total hip prostheses of thirteen patients. Synovial lining capsular tissues from thirteen patients with end-stage degenerative joint disease were used as controls. After homogenization, twenty-nine cytokines were quantified with use of high-throughput protein chips.

RESULTS

IL-6 and IL-8 were found consistently in failed joint replacement tissues, reaffirming their prominent role in osteoclastogenesis and end-stage bone resorption. High levels of interferon-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by interferon-gamma (MIG), both chemoattractants of activated Th1 lymphocytes, were also detected. Soluble intercellular adhesion molecule (sICAM) and transforming growth factor-beta1 (TGF-beta(1)) were not detected universally, nor were TNF-alpha or IL-1. After a twenty-four-hour organ culture, IL-1beta levels increased substantially along with those of other mediators. We measured but did not detect any activators of cytotoxic T-cells, antibody-producing Bcells, or eosinophils involved in delayed-type hypersensitivity. Variations from patient to patient were seen across all cytokines and highlight the unique response of individual patients to their joint replacements.

CONCLUSIONS

In failed total joint replacements in patients with end-stage osteolysis, IL-6 and IL-8 may be the primary drivers of osteoclastogenesis. The presence of IP-10 and MIG imply a role for T-cells, while TGF-beta(1) and sICAM may represent a systemic attempt to modulate the inflammation. TNF-alpha and IL-1 do not appear to play a major role in the end stages of the disease.