PMID- 11229465 OWN - NLM STAT- MEDLINE DCOM- 20010322 LR - 20181130 IS - 0004-3591 (Print) IS - 0004-3591 (Linking) VI - 44 IP - 2 DP - 2001 Feb TI - Effects of intraarticular glucocorticoids on macrophage infiltration and mediators of joint damage in osteoarthritis synovial membranes: findings in a double-blind, placebo-controlled study. PG - 343-50 AB - 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. CONCLUSION: 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. FAU - Young, L AU - Young L AD - Prince of Wales Hospital, Sydney, New South Wales, Australia. FAU - Katrib, A AU - Katrib A FAU - Cuello, C AU - Cuello C FAU - Vollmer-Conna, U AU - Vollmer-Conna U FAU - Bertouch, J V AU - Bertouch JV FAU - Roberts-Thomson, P J AU - Roberts-Thomson PJ FAU - Ahern, M J AU - Ahern MJ FAU - Smith, M D AU - Smith MD FAU - Youssef, P P AU - Youssef PP LA - eng PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL3) RN - 0 (Chemokine CCL4) RN - 0 (Glucocorticoids) RN - 0 (Inflammation Mediators) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (Matrix Metalloproteinase Inhibitors) RN - 0 (Placebos) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - 43502P7F0P (Methylprednisolone Acetate) RN - EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated) RN - EC 3.4.24.- (Metalloendopeptidases) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) RN - X4W7ZR7023 (Methylprednisolone) SB - IM MH - Aged MH - Cell Movement/drug effects MH - Chemokine CCL2/biosynthesis MH - Chemokine CCL3 MH - Chemokine CCL4 MH - Double-Blind Method MH - Female MH - Glucocorticoids/*administration & dosage/pharmacology MH - Humans MH - Immunohistochemistry MH - Inflammation Mediators/pharmacology MH - Injections, Intra-Articular MH - Macrophage Inflammatory Proteins/biosynthesis MH - Macrophages/cytology MH - Male MH - Matrix Metalloproteinase 1/biosynthesis MH - Matrix Metalloproteinase Inhibitors MH - Matrix Metalloproteinases, Membrane-Associated MH - Metalloendopeptidases/antagonists & inhibitors/biosynthesis MH - Methylprednisolone/*analogs & derivatives MH - Methylprednisolone Acetate MH - Middle Aged MH - Osteoarthritis/pathology MH - Placebos MH - Synovial Membrane/chemistry/drug effects MH - Time Factors MH - Tissue Inhibitor of Metalloproteinase-1/biosynthesis MH - Tissue Inhibitor of Metalloproteinase-2/biosynthesis EDAT- 2001/03/07 10:00 MHDA- 2001/03/27 10:01 CRDT- 2001/03/07 10:00 PHST- 2001/03/07 10:00 [pubmed] PHST- 2001/03/27 10:01 [medline] PHST- 2001/03/07 10:00 [entrez] AID - 10.1002/1529-0131(200102)44:2<343::AID-ANR52>3.0.CO;2-Q [doi] PST - ppublish SO - Arthritis Rheum. 2001 Feb;44(2):343-50. doi: 10.1002/1529-0131(200102)44:2<343::AID-ANR52>3.0.CO;2-Q.