Abstract
Tumor necrosis factor-α (TNF-α) 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-α blocking agent, etanercept, the serum levels of the cytokine interleukin-15 (IL-15) and the chemokines growth-regulated protein-α (Gro-α), and interferon-γ 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-α, 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-α 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-α. TNF-α 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.
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Acknowledgments
In this study, I appreciate the cooperation of the division of host defense at the department of infectious disease in Hamamatsu University School of Medicine for the measurement of the levels of a cytokine and chemokines.
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Ichikawa, T., Kageyama, Y., Kobayashi, H. et al. Etanercept treatment reduces the serum levels of interleukin-15 and interferon-gamma inducible protein-10 in patients with rheumatoid arthritis. Rheumatol Int 30, 725–730 (2010). https://doi.org/10.1007/s00296-009-1356-y
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DOI: https://doi.org/10.1007/s00296-009-1356-y