Etanercept reduces the serum levels of macrophage chemotactic protein-1 in patients with rheumatoid arthritis

• Published in: Modern rheumatology Vol. 19; no. 4; pp. 372 - 378
• Main Authors: Kageyama, Yasunori, Kobayashi, Hayato, Kato, Norihiko, Shimazu, Masahiro
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.08.2009; Informa Healthcare
• Subjects: Aged; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - physiopathology; C-Reactive Protein - analysis; Cells, Cultured; Chemokine CCL2 - blood; Chemokine CCL2 - drug effects; Chemokine CCL5 - blood; Chemokine CCL5 - drug effects; Cytokines; Drug therapy; Etanercept; Female; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Granzymes - blood; Granzymes - drug effects; Humans; Immunoglobulin G - therapeutic use; Male; Medicine; Medicine & Public Health; Original Article; Orthopedics; Receptors, Tumor Necrosis Factor - therapeutic use; Rheumatoid arthritis; Rheumatology; Severity of Illness Index; Synovial Membrane - drug effects; Synovial Membrane - metabolism; Synovial Membrane - pathology; Tumor Necrosis Factor-alpha - pharmacology; Etanercept; Rheumatoid arthritis; Monocyte chemotactic protein-1
• ISSN: 1439-7595; 1439-7609
• DOI: 10.1007/s10165-009-0175-z

This study was performed to analyze the effect of etanercept, the soluble tumor necrosis factor-α (TNF-α) receptor, on the serum levels of several chemokines including monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T expressed and presumably secreted (RANTES), and granzyme B in rheumatoid arthritis (RA) patients. Twenty-eight patients with RA were administered etanercept once or twice a week for more than 6 months. Clinical and laboratory parameters were measured and serum levels of MCP-1, RANTES, and granzyme B were determined using enzyme-linked immunosorbent assay (ELISA) kits at baseline and at 3 and 6 months after the initial treatment. In addition, the levels of MCP-1, RANTES, and granzyme B produced by cultured synovial cells stimulated with TNF-α were measured. A significant decrease in serum MCP-1 levels was observed at 3 and 6 months after initial treatment with etanercept. Serum RANTES and granzyme B levels did not show significant changes. TNF-α induced MCP-1, RANTES, and granzyme B production in cultured synovial cells from RA patients. Serum MCP-1 levels were significantly correlated with the disease activity scores of 28 joints combined with CRP (DAS28-CRP), indicating the role of MCP-1 in the pathogenesis of rheumatoid inflammation. This study demonstrated that a reduction of MCP-1 production in RA patients was a newly determined effect of etanercept. Another cascade not associated with TNF-α may induce granzyme B and RANTES production in RA patients.