Simvastatin Inhibits Production of IL-6 and IL-8 and Cell Proliferation Induced by TNF-α in the Fibroblast-Like Synoviocytes from RA Patients

• Published in: Nihon Rinsho Men'eki Gakkai Sokai Shorokushu Vol. 33; p. 87
• Main Authors: 三村, 俊英, 上川, 哲平, 阿達, 大介, 秋葉, 春彦, 秋山, 雄次, 平野, 資晴, 金, 潤澤, 横田, 和浩, 吉田, 佳弘, 石橋, 俊子, 竹石, 美智雄
• Format: Journal Article
• Language: Japanese
• Published: 日本臨床免疫学会 2005; The Japan Society for Clinical Immunology
• Subjects: 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor; Enzyme-linked immunosorbent assay; Fibroblast-like synoviocytes; Interleukin-6 and Interleukin-8; Real-time polymerase chain reaction
• ISSN: 1880-3296
• DOI: 10.14906/jscisho.33.0.87.0

Purpose: We previously reported 10 mg of simvastatin significantly reduced disease activity in active RA patients with hypercholesterolemia. In this study, we investigated the effect of physiological dose of simvastatin on IL-6 and IL-8 production and cell proliferation of RA fibroblast-like synoviocytes (FLS) induced by TNF-α. Methods: FLS were isolated from the synovial tissues of 12 RA patients on the occasion of joint replacement. RA FLS were cultured with or without 0.05-10 μM of simvastatin for 12 h. mRNAs expression and secreted proteins of IL-6 and IL-8 were quantitated by real-time PCR and ELISA, respectively. The cell proliferation of FLS induced by TNF-α was determined by MTT assay. Results: mRNA expression of IL-6 and IL-8 in FLS were inhibited by addition of simvastatin in a dose-dependent manner. IL-6 and IL-8 in the FLS culture medium were decreased by simvastatin in a time-dependent as well as a dose-dependent manner. Additionally, simvastatin inhibited proliferation of FLS induced by TNF-α. Conclusions: Those results suggest that the beneficial effect of simvastatin in RA patients may be through inhibition of IL-6, IL-8 and cell-proliferation in FLS.