Tissue responses to debris formed by abrasion of polymethylmethacrylate
(PMMA) spacers at two-stage revision arthroplasty for prosthetic
joint infection are not well described. We hypothesised that PMMA
debris induces immunomodulation in periprosthetic tissues. Samples of tissue were taken during 35 two-stage revision arthroplasties
(nine total hip and 26 total knee arthroplasties) in patients whose
mean age was 67 years (44 to 85). Fourier transform infrared microscopy
was used to confirm the presence of PMMA particles. Histomorphometry
was performed using Sudan Red and Haematoxylin-Eosin staining.
CD-68, CD-20, CD-11(c), CD-3 and IL-17 antibodies were used to immunophenotype
the inflammatory cells. All slides were scored semi-quantitatively
using the modified Willert scoring system.Aims
Patients and Methods
The peri-prosthetic tissue response to wear debris
is complex and influenced by various factors including the size, area
and number of particles. We hypothesised that the ‘biologically
active area’ of all metal wear particles may predict the type of
peri-prosthetic tissue response. Peri-prosthetic tissue was sampled from 21 patients undergoing
revision of a small diameter metal-on-metal (MoM) total hip arthroplasty
(THA) for aseptic loosening. An enzymatic protocol was used for
tissue digestion and scanning electron microscope was used to characterise
particles. Equivalent circle diameters and particle areas were calculated.
Histomorphometric analyses were performed on all tissue specimens.
Aspirates of synovial fluid were collected for analysis of the cytokine
profile analysis, and compared with a control group of patients
undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene
arthroplasty (n = 6). The overall distribution of the size and area of the particles
in both lymphocyte and
non-lymphocyte-dominated responses were similar; however, the subgroup
with lymphocyte-dominated peri-prosthetic tissue responses had a
significantly larger total number of particles. 14 cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10,
IL-13, IL-17, interferon (IFN)-γ, and IFN-gamma-inducible protein
10), chemokines (macrophage inflammatory protein (MIP)-1α and MIP-1ß),
and growth factors (granulocyte macrophage colony stimulating factor
(GM-CSF) and platelet derived growth factor) were detected at significantly higher
levels in patients with metal wear debris compared with the control
group. Significantly higher levels for IL-1ß, IL-5, IL-10 and GM-CSF
were found in the subgroup of tissues from failed MoM THAs with
a lymphocyte-dominated peri-prosthetic response compared with those
without this response. These results suggest that the ‘biologically active area’ predicts
the type of
peri-prosthetic tissue response. The cytokines IL-1ß, IL-5, IL-10,
and GM-CSF are associated with lymphocyte-dominated tissue responses
from failed small-diameter MoM THA. Cite this article:
