Etanercept treatment reduces the serum levels of interleukin-15 and interferon-gamma inducible protein-10 in patients with rheumatoid arthritis.
Tumor necrosis factor-alpha (TNF-alpha) has an essential role in the pathogenesis of rheumatoid arthritis (RA) and has been known to induce the production of several inflammatory molecules in vivo. To analyze in vivo the active mechanism of the TNF-alpha blocking agent, etanercept, the serum levels of the cytokine interleukin-15 (IL-15) and the chemokines growth-regulated protein-alpha (Gro-alpha), and interferon-gamma inducible protein-10 (IP-10) in RA patients were measured. Twenty-two patients with RA were administered etanercept once or twice a week for more than 6 months. The clinical and laboratory parameters were measured and serum levels of IL-15, Gro-alpha, and IP-10 were determined using enzyme-linked immunosorbent assay (ELISA) kits at the baseline and at 3 and 6 months after the initial treatment. Additionally, the production of IL-15 and IP-10 by cultured synovial cells stimulated with TNF-alpha from RA patients was determined by ELISA. A significant decrease in serum levels of IL-15 and IP-10 was observed at 3 and 6 months after initial treatment with etanercept, but not in those of Gro-alpha. TNF-alpha induced production of IP-10, but not IL-15 in cultured synovial cells from RA patients. This study demonstrated for the first time the reduction of IP-10 and IL-15 production in RA patients as active mechanisms of etanercept.
Ichikawa
Tetsuya
T
Department of Orthopaedic Surgery, Narita Memorial Hospital, 78 Shirakawa-cho, Toyohashi, 441-8021, Japan.
Kageyama
Yasunori
Y
Kobayashi
Hayato
H
Kato
Norihiko
N
Tsujimura
Kunio
K
Koide
Yukio
Y
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000037:antagonists & inhibitors / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019409:Interleukin-15 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood
C475829:CXCL1 protein, human; C114753:CXCL10 protein, human; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept