Expression of chemokines and matrix metalloproteinases in early rheumatoid arthritis

Objective. To compare macrophage infiltration and expression of chemokines and matrix metalloproteinases (MMPs) in synovial tissue between patients with early and long-standing rheumatoid arthritis (RA). Methods. Knee synovial biopsies were taken from 22 patients with early (<1 yr) and 22 patients with long-standing (>5 yr) RA and immunostained with antibodies specific for CD68; macrophage inflammatory protein (MIP)-1 alpha and monocyte chemoattractant protein (MCP)-1; MMP-1 and -3 and the tissue inhibitors of metalloproteinases (TIMP)-1 and -2. Immunostaining was quantified using a colour video image analysis system. Results. CD68+ macrophage infiltration and the expression of MIP-1 alpha, MCP-1, MMP-1, MMP-3, TIMP-1, and TIMP-2 were observed in synovial tissue of patients with early RA. In long-standing RA, there was a further increase in CD68+ macrophage infiltration and MIP-1 alpha expression in the synovial lining layer. CD68 expression correlated with MIP-1 alpha (R=0.39, P=0.01), but not with MCP-1 expression. Conclusion. Macrophage accumulation, and the expression of chemokines and MMPs in synovial tissue occur in early RA. Targeting chemokines which play a role in the migration of macrophages into the joints may be of therapeutic benefit in RA patients.