Effects of intraarticular glucocorticoids on macrophage infiltration and mediators of joint damage in osteoarthritis synovial membranes: findings in a double-blind, placebo-controlled study

Arthritis Rheum. 2001 Feb;44(2):343-50. doi: 10.1002/1529-0131(200102)44:2<343::AID-ANR52>3.0.CO;2-Q.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Movement / drug effects
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL3
  • Chemokine CCL4
  • Double-Blind Method
  • Female
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / pharmacology
  • Humans
  • Immunohistochemistry
  • Inflammation Mediators / pharmacology
  • Injections, Intra-Articular
  • Macrophage Inflammatory Proteins / biosynthesis
  • Macrophages / cytology
  • Male
  • Matrix Metalloproteinase 1 / biosynthesis
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / biosynthesis
  • Methylprednisolone / analogs & derivatives*
  • Methylprednisolone Acetate
  • Middle Aged
  • Osteoarthritis / pathology
  • Placebos
  • Synovial Membrane / chemistry
  • Synovial Membrane / drug effects
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis


  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Glucocorticoids
  • Inflammation Mediators
  • Macrophage Inflammatory Proteins
  • Matrix Metalloproteinase Inhibitors
  • Placebos
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Methylprednisolone Acetate
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 1
  • Methylprednisolone