Etanercept reduces the serum levels of macrophage chemotactic protein-1 in patients with rheumatoid arthritis.
This study was performed to analyze the effect of etanercept, the soluble tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha 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-alpha may induce granzyme B and RANTES production in RA patients.
Kageyama
Yasunori
Y
Department of Orthopaedic Surgery, Heisei Memorial Hospital, 123-1 Mizugami, Fujieda 426-8662, Japan. Tsukatonpipi@nifty.com
Kobayashi
Hayato
H
Kato
Norihiko
N
Shimazu
Masahiro
M
D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D002097:C-Reactive Protein / Q000032:analysis; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood / Q000187:drug effects*; D018946:Chemokine CCL5 / Q000097:blood / Q000187:drug effects; D000068800:Etanercept; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053804:Granzymes / Q000097:blood / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018501:Antirheumatic Agents; C111835:CCL2 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D053804:Granzymes; D000068800:Etanercept