Is monocyte chemotactic protein 1 elevated in aseptic loosening of TKA? A pilot study

Abstract

Background: Failure of TKA from aseptic loosening is a growing concern, as TKA is performed with increasing frequency. Loosening is multifactorial and may be associated with elevated inflammatory cytokines in addition to biomechanical failure.

Questions/purposes: We asked whether proinflammatory cytokines and chemokines are elevated in synovial fluid from patients undergoing revision surgery as compared to those with osteoarthritis (OA) or rheumatoid arthritis (RA).

Methods: We obtained synovial fluid samples from 20 patients: six with aseptic loosening of TKA (all with bone loss), 10 with primary OA, and four with RA. A panel of cytokines/chemokines was screened using a SearchLight(®) Array (Pierce Biotechnology, Rockford, IL, USA) in one revision sample. Using these data, we assayed the synovial fluids for monocyte chemotactic protein 1 (MCP-1) by ELISA.

Results: We observed an increase in synovial MCP-1 levels in samples from patients planned for TKA revision compared to those with OA or RA. In patients undergoing revision arthroplasty, the mean (± SD) MCP-1 concentration was 21,233 ± 18,966 pg/mL (range, 1550-50,657 pg/mL; n = 6). In patients with OA, the mean MCP-1 level was 3012 ± 3321 pg/mL. In patients with RA, the mean MCP-1 concentration was 690 ± 561 pg/mL.

Conclusions: All patients undergoing revision TKA showed elevated concentrations of MCP-1 compared to patients with OA and RA, suggesting MCP-1 may serve as a potential marker or predictor of bone loss in patients undergoing revision surgery.

Clinical relevance: MCP-1 may be a novel biomarker in patients showing early symptoms of aseptic loosening of TKA.

Fig. 1A–D

Elevated levels of MCP-1 occurred in patients undergoing revision surgery and some patients with OA. Graphs show the MCP-1 concentrations in synovial fluid of (A) patients undergoing revision surgery for aseptic loosening of TKA (n = 6), (B) patients with OA undergoing primary TKA (n = 10), and (C) patients with RA undergoing primary TKA (n = 4). All samples were analyzed in triplicate, and SDs are shown. (D) A compilation of MCP-1 data shows elevated MCP-1 in patients undergoing revision TKA for aseptic loosening (n = 6) as compared to patients with OA (n = 10) or RA (n = 4) undergoing primary TKA.

Fig. 2

Screening of a large panel of cytokines and chemokines identifies high levels of MCP-1 in synovial fluid from a patient undergoing revision surgery for aseptic loosening of TKA. A SearchLight^® Array (Pierce Biotechnology) was performed using 50 μL of synovial fluid from one patient undergoing revision (Patient 1). Concentrations of the indicated cytokines or chemokines are indicated. IFN-γ = interferon γ; IP-10 = 10-kDa IFN-γ-induced protein; MIP-1α = macrophage inflammatory protein 1α.