Rheumatology 2000; 39: 1067-1073
© 2000 British Society for Rheumatology
The effects of pulse methylprednisolone on matrix metalloproteinase and tissue inhibitor of metalloproteinase-1 expression in rheumatoid arthritis
1 Rheumatology Unit, Prince of Wales Hospital, Sydney,
2 Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney,
3 Department of Clinical Immunology and Rheumatology Unit, Flinders Medical Centre, Flinders Drive, Bedford Park, Adelaide,
4 Department of Medicine, Flinders University, Bedford Park, Adelaide and the Repatriation General Hospital, Adelaide, South Australia, Australia
Objective. To investigate the effects of a 1000 mg i.v. pulse of methylprednisolone succinate (pulse therapy) on the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the synovial membrane of the knee in patients with rheumatoid arthritis (RA).
Methods. Sequential arthroscopic biopsies of the knee were taken before and 24 h after pulse therapy (11 patients), at disease relapse (three patients) and after retreatment with pulse therapy (one patient). Immunoperoxidase staining for MMP-1 (interstitial collagenase), MMP-3 (stromelysin-1) and TIMP-1 was performed and the immunoreactive staining quantified by colour video image analysis.
Results. In the synovial lining layer, MMP-1 and TIMP-1 immunostaining was reduced by a mean of 47% (P = 0.02) and 72% (P = 0.05), respectively, 24 h after pulse methylprednisolone therapy. In the synovial sublining layer, MMP-1 was reduced by a mean of 51% (P = 0.08) and TIMP-1 by a mean of 73% (P = 0.02) 24 h after pulse methylprednisolone therapy. There was no change in MMP-3 staining in the synovial lining or sublining layer.
Conclusions. High-dose pulse methylprednisolone therapy is associated with a rapid (within 24 h) and substantial decrease in the expression of MMP-1 and TIMP-1 but not MMP-3 in the synovial membrane in RA.
KEY WORDS: Rheumatoid arthritis, Matrix metalloproteinases, TIMP, Corticosteroids.
Correspondence to: P. P. Youssef, Inflammation Research Unit, School of Pathology, Wallace Wurth Building, University of New South Wales, Sydney 2052, Australia.
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