P. Wong et al., The effects of pulse methylprednisolone on matrix metalloproteinase and tissue inhibitor of metalloproteinase-1 expression in rheumatoid arthritis, RHEUMATOLOG, 39(10), 2000, pp. 1067-1073
Objective. To investigate the effects of a 1000 mg i.v. pulse of methylpred
nisolone succinate (pulse therapy) on the expression of matrix metalloprote
inases (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 TI
MP-1 was performed and the immunoreactive staining quantified by colour vid
eo 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, MM
P-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 a
nd TIMP-1 but not MMP-3 in the synovial membrane in RA.