The effects of pulse methylprednisolone on matrix metalloproteinase and tissue inhibitor of metalloproteinase-1 expression in rheumatoid arthritis.
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.
Wong
P
P
Rheumatology Unit, Prince of Wales Hospital, Sydney, Australia.
Cuello
C
C
Bertouch
J V
JV
Roberts-Thomson
P J
PJ
Ahern
M J
MJ
Smith
M D
MD
Youssef
P P
PP
D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008776:Methylprednisolone Hemisuccinate / Q000627:therapeutic use*; D008875:Middle Aged; D013583:Synovial Membrane / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D008776:Methylprednisolone Hemisuccinate; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1