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IL-ß, IL-1RA, MMP-1 AND TIMP-2 MRNA AND PROTEIN IN TOTAL JOINT ARTHROPLASTY.



Abstract

Methods: Sixty pseudo-capsular tissues from loose shoulder, hip and knee (20 each) arthroplasties and 30 capsular tissues from primary total joint arthroplasty (TJA) patients (10 each; 12 rheumatoid arthritis [RA], 18 osteo-arthrosis [OA]) were investigated for mRNA and protein expressions of IL-1ß (interleukin-1 b, IL-1Ra (interleukin-1 receptor antagonist), MMP 1 (matrix matalloproteinase-1)-, TIMP 2 (tissue inhibitor of MMPs-2) using in situ hybridisation and immunohistochemistry. Polyethylene and metal debris in the same sections were semi-quantified simultaneously.

Results: IL-1ß mRNA and proteins were expressed in most RA primary and revision tissues and were less expressed in OA primary tissues. In contrast, IL-1Ra mRNA was found in most primary OA tissues and less in RA primary and the revision tissues. The ratio of staining intensities of IL-1ß/IL-1Ra mRNA was higher in revision and primary RA tissues compared with the primary OA tissues. MMP-1 protein expression was correlated with the IL-1ß/IL-1Ra ratio. Polyethylene (PE) debris was found in 56 out of 60 of the revision tissues. Their sizes were different in the hip (mainly small, < 30 mm in diameter), the knee (mainly large, > 300 mm) and the shoulder (all sizes). The expressions of the detected factors were highly correlated with the concentration of the PE debris but with not their sizes.

Conclusions: The high ratio of IL-1ß/IL-1Ra in primary RA and revision tissues and its correlation with MMP-1 expression and PE debris concentration indicated that an over-expression of IL-1ß and/or regulation downwards of IL-1Ra is an important event in inflammatory disorders and the foreign body reaction in TJA. A therapeutic strategy with IL-1Ra, that has been considered in RA treatment may thus contribute to the longevity of prosthesis of a TJA.

The abstracts were prepared by Professor A. J. Thurston. Correspondence should be addressed to him at the Department of Surgery, Wellington School of Medicine, PO Box 7343, Wellington South, New Zealand