Effects of intraarticular glucocorticoids on macrophage infiltration and mediators of joint damage in osteoarthritis synovial membranes: findings in a double-blind, placebo-controlled study.
OBJECTIVE
To investigate the effects of intraarticular glucocorticoid treatment on macrophage infiltration, the expression of the chemokines monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1alpha (MIP-1alpha), and the expression of matrix metalloproteinases 1 and 3 (MMPs 1 and 3) and their inhibitors, the tissue inhibitors of metalloproteinases 1 and 2 (TIMPs 1 and 2), in osteoarthritis (OA) synovial membranes.


METHODS
Forty patients underwent arthroscopic biopsy before and 1 month after intraarticular injection of glucocorticoids. Twenty-one patients received 120 mg of methylprednisolone acetate (Depo-Medrol; Upjohn, Kalamazoo, MI), and 20 patients received placebo (1 patient received placebo in 1 knee and methylprednisolone acetate in the other). Immunoperoxidase staining for the expression of CD68, MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 was performed, and the immunostaining was quantified by color video image analysis.


RESULTS
CD68, MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 immunostaining was observed in all synovial membranes. Intraarticular glucocorticoid treatment was associated with a small (30%) but statistically significant (P = 0.048) reduction in CD68+ macrophage staining in the synovial lining layer, but there was no change in the CD68 expression in the synovial sublining layer. No significant differences were observed for MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 immunostaining in the synovial lining or sublining layers.


CONCLUSIONS
Intraarticular glucocorticoids may reduce CD68+ macrophage infiltration into the synovial lining layer, but not the expression of MCP-1, MIP-1alpha, MMP-1, MMP-3, TIMP-1, and TIMP-2 in the synovial membrane, in patients with OA.
Prince of Wales Hospital, Sydney, New South Wales, Australia.
L
L
Young
A
A
Katrib
C
C
Cuello
U
U
Vollmer-Conna
J V
JV
Bertouch
P J
PJ
Roberts-Thomson
M J
MJ
Ahern
M D
MD
Smith
P P
PP
Youssef
D000368:Aged; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000494:pharmacology; D007270:Injections, Intra-Articular; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008775:Methylprednisolone / Q000031:analogs & derivatives*; D000077555:Methylprednisolone Acetate; D008875:Middle Aged; D010003:Osteoarthritis / Q000473:pathology; D010919:Placebos; D013583:Synovial Membrane / Q000737:chemistry / Q000187:drug effects; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D005938:Glucocorticoids; D018836:Inflammation Mediators; D019402:Macrophage Inflammatory Proteins; D061965:Matrix Metalloproteinase Inhibitors; D010919:Placebos; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D000077555:Methylprednisolone Acetate; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020781:Matrix Metalloproteinase 1; D008775:Methylprednisolone