関節リウマチにおけるアディポサイトカインの臨床的意義

• 研究課題/領域番号: 20591177
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 膠原病・アレルギー内科学
• 研究機関: 東邦大学
• 研究代表者: 川合 眞一 東邦大学, 医学部, 教授 (70129401)
• 研究期間 (年度): 2008 – 2010
• 研究課題ステータス: 完了 (2010年度)
• 配分額: 4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円); 2010年度: 910千円 (直接経費: 700千円、間接経費: 210千円); 2009年度: 1,820千円 (直接経費: 1,400千円、間接経費: 420千円); 2008年度: 1,950千円 (直接経費: 1,500千円、間接経費: 450千円)
• キーワード: リウマチ学 / 関節リウマチ / アディポサイトカイン / rheumatoid arthritis / adipocytokine / adiponectin / synovial fibroblasts

研究概要

脂肪組織はアディポサイトカインと呼ばれる生理活性物質を分泌しており、申請者らは関節リウマチ(RA)における意義を検討した。中でもアディポネクチンは、ヒト滑膜細胞のIL-8産生(Biochem Biophys Res Commun.2009;378:218-223)やプロスタグランジンE2産生(Arthritis Rheum.2010;62:1641-1649)を増加させた。一方、RA患者のアディポネクチン、レジスチン、レプチン血清濃度は健常人よりも増加していた(Intern Med.2011;50:269-275)。即ち、アディポサイトカインはRAの病態形成に何らかの関与をしていることを示唆している。

研究成果

• [雑誌論文] Elevated serum levels of resistin, leptin, and adiponectin are associated with C-reactive protein and also other clinical conditions in rheumatoid arthritis. (2011)
  • 著者名/発表者名: Yoshino T, Kusunoki N, Tanaka N, Kaneko K, Kusunoki Y, Endo H, Hasunuma T, Kawai S.
  • 雑誌名: Intern Med. 50 ページ: 269-275
  • NAID: 130000413109
  • 査読あり
• [雑誌論文] Clinical and radiological features of acute-onset diffuse interstitial lung diseases in patients with rheumatoid arthritis receiving treatment with biological agents : importance of pneumocystis pneumonia in Japan revealed by a multicenter study. (2011)
  • 著者名/発表者名: Kameda H, Tokuda H, Sakai F, Johkoh T, Mori S, Yoshida Y, Takayanagi N, Taki H, Hasegawa Y, Hatta K, Yamanaka H, Dohi M, Hashimoto S, Yamada H, Kawai S, Takeuchi T, Tateda K, Goto H.
  • 雑誌名: Intern Med. 50 ページ: 305-313
  • NAID: 130000413114
  • 査読あり
• [雑誌論文] anti-interleukin-6-receptor antibody (tocilizumab) monotherapy is more effective in slowing radiographic progression in patients with rheumatoid arthritis at high baseline risk for structural damage evaluated with levels of biomarkers, radiography, and BMI : data from the SAMURAI study. (2011)
  • 著者名/発表者名: Hashimoto J, Garnero P, van der Heijde D, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Yoshikawa H, Nishimoto N. Humanized
  • 雑誌名: Mod Rheumatol. 21 ページ: 10-15
  • 査読あり
• [雑誌論文] Humanized anti-interleukin-6-receptor antibody (tocilizumab) monotherapy is more effective in slowing radiographic progression in patients with rheumatoid arthritis at high baseline risk for structural damage evaluated with levels of biomarkers, radiography, and BMI : data from the SAMURAI study. (2011)
  • 著者名/発表者名: Hashimoto J, Kawai S, et al.
  • 雑誌名: Mod Rheumatol. 巻: 21 ページ: 10-15
  • NAID: 10029361106
  • 査読あり
• [雑誌論文] Elevated serum levels of resistin, leptin, and adiponectin are associated with C-reactive protein and also other clinical conditions in rheumatoid arthritis. (2011)
  • 著者名/発表者名: Yoshino T, Kawai S, et al.
  • 雑誌名: Intern Med. 巻: 50 ページ: 269-275
  • NAID: 130000413109
  • 査読あり
• [雑誌論文] Clinical and radiological features of acute-onset diffuse interstitial lung diseases in patients with rheumatoid arthritis receiving treatment with biological agents importance of pneumocystis pneumonia in Japan revealed by a multicenter study. (2011)
  • 著者名/発表者名: Kameda H, Kawai S, et al.
  • 雑誌名: Intern Med. 巻: 50 ページ: 305-313
  • NAID: 130000413114
  • 査読あり
• [雑誌論文] Efficacy and safety of additional use of tacrolimus in early rheumatoid arthritis patients with inadequate response to DMARDs-a multicenter, double-blind, parallel-group trial. (2011)
  • 著者名/発表者名: Kawai S, et al
  • 雑誌名: Mod Rheumatol. 巻: (in press)
  • 査読あり
• [雑誌論文] Exacerbation of adult-onset Still's disease, possibly related to elevation of serum tumor necrosis factor-α after etanercept administration. (2010)
  • 著者名/発表者名: Kaneko K, Kaburaki M, Muraoka S, Tanaka N, Yamamoto T, Kusunoki Y, Abe H, Endo H, Kawai S.
  • 雑誌名: Int J Rheum Dis. 13
  • 査読あり
• [雑誌論文] Efficacy and safety of ketoprofen patch in patients with rheumatoid arthritis : a randomized, double-blind, placebo-controlled study. (2010)
  • 著者名/発表者名: Kawai S, Uchida E, Kondo M, Ohno S, Obata J, Nawata Y, Sugimoto K, Oribe M, Nagaya I.
  • 雑誌名: J Clin Pharmacol. 50 ページ: 1171-1179
  • 査読あり
• [雑誌論文] Systemic lupus erythematosus complicated by recurrent pneumothorax : case report and literature review. (2010)
  • 著者名/発表者名: Tanaka N, Kusunoki Y, Kaneko K, Yamamoto T, Kaburaki M, Muraoka S, Abe H, Endo H, Sato D, Homma S, Shibuya K, Kawai S.
  • 雑誌名: Jpn J Clin Immunol. 33 ページ: 162-168
  • NAID: 10026543359
  • 査読あり
• [雑誌論文] Adiponectin stimulates prostaglandin E_2 production in rheumatoid synovial fibroblasts. (2010)
  • 著者名/発表者名: Kusunoki N, Kitahara K, Kojima F, Tanaka N, Kaneko K, Endo H, Suguro T, Kawai S.
  • 雑誌名: Arthritis Rheum. 62 ページ: 1641-1649
  • 査読あり
• [雑誌論文] Clinical activities after 12 weeks of treatment with non-biologics in early rheumatoid arthritis may predict the articular destruction 2 years later. (2010)
  • 著者名/発表者名: Ichikawa Y, Saito T, Yamanaka H, Akizuki M, Kondo H, Kobayashi S, Oshima H, Kawai S, et al.
  • 雑誌名: J Rheumatol. 37 ページ: 723-729
  • 査読あり
• [雑誌論文] Clinical activities after 12 weeks of treatment with non-biologics in early rheumatoid arthritis may predict the articular destruction 2 years later. (2010)
  • 著者名/発表者名: Ichikawa Y, Kawai S, et al
  • 雑誌名: J Rheumatol. 巻: 37 ページ: 723-729
  • 査読あり
• [雑誌論文] Adiponectin stimulates prostaglandin E2 production in rheumatoid synovial fibroblasts. (2010)
  • 著者名/発表者名: Kusunoki N, Kawai S, et al.
  • 雑誌名: Arthritis Rheum. 巻: 62 ページ: 1641-1649
  • NAID: 130006950120
  • 査読あり
• [雑誌論文] Systemic lupus erythematosus complicated by recurrent pneumothorax : case report and literature review. (2010)
  • 著者名/発表者名: Tanaka N, Kawai S, et al.
  • 雑誌名: Jpn J Clin Immunol. 巻: 33 ページ: 162-168
  • NAID: 10026543359
  • 査読あり
• [雑誌論文] Efficacy and safety of ketoprofen patch in patients with rheumatoid arthritis : a randomized, double-blind, placebo controlled study. (2010)
  • 著者名/発表者名: Kawai S, et al.
  • 雑誌名: J Clin Pharmacol. 巻: 50 ページ: 1171-1179
  • 査読あり
• [雑誌論文] Exacerbation of adult-onset Still's disease, possibly related to elevation of serum tumor necrosis factor after etanercept administration. (2010)
  • 著者名/発表者名: Kaneko K, Kawai S, et al.
  • 雑誌名: Int J Rheum Dis. 巻: 13 ページ: 67-69
  • 査読あり
• [雑誌論文] Tacrolimus therapy for systemic lupus erythematosus without renal involvement : a preliminary retrospective study. (2009)
  • 著者名/発表者名: Kusunoki Y, Tanaka N, Kaneko K, Yamamoto T, Endo H, Kawai S.
  • 雑誌名: Mod Rheumatol. 19 ページ: 616-621
  • NAID: 10027167729
  • 査読あり
• [雑誌論文] Efficacy and safety of tacrolimus for lupus nephritis : a placebo-controlled double-blind multicenter study. (2009)
  • 著者名/発表者名: Miyasaka N, Kawai S, Hashimoto H.
  • 雑誌名: Mod Rheumatol. 19 ページ: 606-615
  • NAID: 10027167694
  • 査読あり
• [雑誌論文] Long-term safety and efficacy of tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study) : evidence of safety and efficacy in a 5-year extension study. (2009)
  • 著者名/発表者名: Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J.
  • 雑誌名: Ann Rheum Dis. 68 ページ: 1580-1584
  • 査読あり
• [雑誌論文] Japan College of Rheumatology 2009 guidelines for the use of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, in rheumatoid arthritis. (2009)
  • 著者名/発表者名: Koike R, Harigai M, Atsumi T, Amano K, Kawai S, Saito K, Saito T, Yamamura M, Matsubara T, Miyasaka N.
  • 雑誌名: Mod Rheumatol. 19 ページ: 351-357
  • NAID: 10025113303
  • 査読あり
• [雑誌論文] Erythrocyte methotrexate-polyglutamate assay using fluorescence polarization immunoassay technique : application to the monitoring of patients with rheumatoid arthritis. (2009)
  • 著者名/発表者名: Inoue S, Hashiguchi M, Kawai S, Mochizuki M.
  • 雑誌名: Yakugaku Zasshi. 129 ページ: 1001-1005
  • NAID: 130000135996
  • 査読あり
• [雑誌論文] Prostaglandin E_2 differentially modulates proinflammatory/prodestructive effects of TNF-alpha on synovial fibroblasts via specific E prostanoid receptors/cAMP. (2009)
  • 著者名/発表者名: Kunisch E, Jansen A, Kojima F, Loffler I, Kapoor M, Kawai S, Rubio I, Crofford LJ, Kinne RW.
  • 雑誌名: J Immunol. 183 ページ: 1328-1336
  • 査読あり
• [雑誌論文] Preliminary study to identify the predictive factors for the response to methotrexate therapy in patients with rheumatoid arthritis. (2009)
  • 著者名/発表者名: Inoue S, Hashiguchi M, Takagi K, Kawai S, Mochizuki M.
  • 雑誌名: Yakugaku Zasshi. 129 ページ: 843-849
  • NAID: 130000135978
  • 査読あり
• [雑誌論文] Prostaglandin E_2 activates RAP1 via EP2/EP4 receptors and cAMP-signaling in rheumatoid synovial fibroblasts : Involvement of EPAC1 and PKA. (2009)
  • 著者名/発表者名: Kojima F, Kapoor M, Kawai S, Yang L, Aronoff DM, Crofford LJ.
  • 雑誌名: Prostaglandins Other Lipid Mediat. 89 ページ: 26-33
  • 査読あり
• [雑誌論文] Pharmacokinetic study and Fcγ receptor gene analysis in 2 patients with rheumatoid arthritis controlled by low-dose infliximab. (2009)
  • 著者名/発表者名: Nishio S, Yamamoto T, Kaneko K, Tanaka-Matsumoto N, Muraoka S, Kaburaki M, Kusunoki Y, Takagi K, Kawai S.
  • 雑誌名: Mod Rheumatol. 19 ページ: 329-333
  • 査読あり
• [雑誌論文] A combination of biochemical markers of cartilage and bone turnover, radiographic damage and body mass index to predict the progression of joint destruction in patients with rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs. (2009)
  • 著者名/発表者名: Hashimoto J, Garnero P, van der Heijde D, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Yoshikawa H, Nishimoto N.
  • 雑誌名: Mod Rheumatol. 19 ページ: 273-282
  • NAID: 10025112961
  • 査読あり
• [雑誌論文] Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI) : significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. (2009)
  • 著者名/発表者名: Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J, Kishimoto T.
  • 雑誌名: Mod Rheumatol 19 ページ: 12-19
  • NAID: 10025111886
  • 査読あり
• [雑誌論文] Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts. (2009)
  • 著者名/発表者名: Kitahara K, Kusunoki N, Kakiuchi T, Suguro T, Kawai S.
  • 雑誌名: Biochem Biophys Res Commun. 378 ページ: 218-223
  • 査読あり
• [雑誌論文] A combination of biochemical markers of cartilage and bone turnover, radiographic damage and body mass index to predict the progression of joint destruction in patients with rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs (2009)
  • 著者名/発表者名: Hashimoto J, Garnero P, van der Heijde D, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Yoshikawa H, Nishimoto N.
  • 雑誌名: Mod Rheumatol 19(3) ページ: 273-282
  • NAID: 10025112961
  • 査読あり
• [雑誌論文] Pharmacokinetic study and Fcγ receptor gene analysis in 2 patients with rheumatoid arthritis controlled by low-dose infliximab (2009)
  • 著者名/発表者名: Nishio S, Yamamoto T, Kaneko K, Tanaka-Matsumoto N, et al
  • 雑誌名: Mod Rheumatol 19(3) ページ: 329-333
  • 査読あり
• [雑誌論文] Prostaglandin E_2 activates RAP1 via EP2/EP4 receptors and cAMP-signaling in rheumatoid synovial fibroblasts : Involvement of EPAC1 and PKA (2009)
  • 著者名/発表者名: Kojima F, Kapoor M, Kawai S, Yang L, Aronoff DM, Crofford LJ.
  • 雑誌名: Prostaglandins Other Lipid Medial 89(1-2) ページ: 26-33
  • 査読あり
• [雑誌論文] Preliminary study to identify the predictive factors for the response to methotrexate therapy in patients with rheumatoid arthritis (2009)
  • 著者名/発表者名: Inoue S, Hashiguchi M, Takagi K, Kawai S, Mochizuki M.
  • 雑誌名: Yakugaku Zasshi 129(7) ページ: 843-849
  • NAID: 130000135978
  • 査読あり
• [雑誌論文] Prostaglandin E_2 differentially modulates proinflammatory/prodestructive effects of TNF-alpha on synovial fibroblasts via specific E prostanoid receptors/cAMP (2009)
  • 著者名/発表者名: Kunisch E, Jansen A, Kojima F, Loffler I, Kapoor M, Kawai S, Rubio I, Crofford LJ, Kinne RW.
  • 雑誌名: J Immunol 183(2) ページ: 1328-1336
  • 査読あり
• [雑誌論文] Erythrocyte methotrexate- polyglutamate assay using fluorescence polarization immunoassay technique : application to the monitoring of patients with rheumatoid arthritis (2009)
  • 著者名/発表者名: Inoue S, Hashiguchi M, Kawai S, Mochizuki M.
  • 雑誌名: Yakugaku Zasshi 129(8) ページ: 1001-1005
  • NAID: 130000135996
  • 査読あり
• [雑誌論文] Japan College of Rheumatology 2009 guidelines for the use of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, in rheumatoid arthritis (2009)
  • 著者名/発表者名: Koike R, Harigai M, Atsumi T, Amano K, Kawai S, Saito K, Saito T, Yamamura M, Matsubara T, Miyasaka N.
  • 雑誌名: Mod Rheumatol 19(4) ページ: 351-357
  • NAID: 10025113303
  • 査読あり
• [雑誌論文] Long-term safety and efficacy of tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis(the STREAM study) : evidence of safety and efficacy in a 5-year extension study (2009)
  • 著者名/発表者名: Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J.
  • 雑誌名: Ann Rheum Dis 68(10) ページ: 1580-1584
  • 査読あり
• [雑誌論文] Efficacy and safety of tacrolimus for lupus nephritis : a placebo-controlled double-blind multicenter study (2009)
  • 著者名/発表者名: Miyasaka N, Kawai S, Hashimoto H.
  • 雑誌名: Mod Rheumatol 19(6) ページ: 606-615
  • NAID: 10027167694
  • 査読あり
• [雑誌論文] Tacrolimus therapy for systemic lupus erythematosus without renal in volvement : a preliminary retrospective study (2009)
  • 著者名/発表者名: Kusunoki Y, Tanaka N, Kaneko K, Yamamoto T, Endo H, Kawai S.
  • 雑誌名: Mod Rheumatol 19(6) ページ: 616-621
  • 査読あり
• [雑誌論文] Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts. (2009)
  • 著者名/発表者名: Kitahara K, et al
  • 雑誌名: Biochem Biophys Res Commun 378 ページ: 218-223
  • 査読あり
• [雑誌論文] Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate(SATORI) : significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. (2009)
  • 著者名/発表者名: Nishimoto N, et al.
  • 雑誌名: Mod Rheumatol 19 ページ: 12-19
  • 査読あり
• [雑誌論文] Pro-apoptotic effect of nonsteroidal anti-inflammatory drugs on synovial fibroblasts. (2008)
  • 著者名/発表者名: Kusunoki N, Yamazaki R, Kawai S.
  • 雑誌名: Mod Rheumatol. 18 ページ: 542-551
  • NAID: 10025111417
  • 査読あり
• [雑誌論文] Safety profile of tacrolimus in patients with rheumatoid arthritis. (2008)
  • 著者名/発表者名: Akimoto K, Kusunoki Y, Nishio S, Takagi K, Kawai S.
  • 雑誌名: Clin Rheumatol. 27 ページ: 1393-1397
  • 査読あり
• [雑誌論文] Clinical value of second and third generation assays of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis. (2008)
  • 著者名/発表者名: Kitahara K, Takagi K, Kusunoki Y, Nishio S, Nozaki T, Inomata H, Takei M, Sawada S, Kawai S.
  • 雑誌名: Ann Rheum Dis. 67 ページ: 1059-1060
  • 査読あり
• [雑誌論文] Safety of long-term tacrolimus therapy for rheumatoid arthritis : an open-label uncontrolled study in non-elderly patients. (2008)
  • 著者名/発表者名: Kawai S, Tanaka K, Ohno I, Utsunomiya K, Seino Y.
  • 雑誌名: Mod Rheumatol. 18 ページ: 345-353
  • NAID: 10021946870
  • 査読あり
• [雑誌論文] Clinical value of second and third generation assays of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis. (2008)
  • 著者名/発表者名: Kitahara K, et al
  • 雑誌名: Ann Rheum Dis 67 ページ: 1059-1060
  • 査読あり
• [雑誌論文] Safty of long-term tacrolimus therapy for rheumatoid arthritis : an open-lebel, uncontrolled study in non-elderly patients. (2008)
  • 著者名/発表者名: Kawai S, et al
  • 雑誌名: Mod Rheumatol 18 ページ: 345-353
  • 査読あり
• [雑誌論文] Safety profile of tacrolimus in patients with rheumatoid arthritis. (2008)
  • 著者名/発表者名: Akimoto K, et al
  • 雑誌名: Clin Rheumatol 27 ページ: 1393-1397
  • 査読あり
• [雑誌論文] Pro-apoptotic effect of nonsteroidal anti-inflammatory drugs on synovial fibroblasts. (2008)
  • 著者名/発表者名: Kusunoki N, et al
  • 雑誌名: Mod Rheumatol 18 ページ: 542-551
  • 査読あり
• [学会発表] Current Condition of Drug Therapy for Rheumatoid Arthritis in Japan. (2008)
  • 著者名/発表者名: Kawai S
  • 学会等名: MEDICAL-EXPO 2008 in APLAR' s World. 13TH Congress of the Asia Pacific League of Associations for Rheumatology.
  • 発表場所: Yokohama, Japan
  • 年月日: 2008-09-23
• [学会発表] Adipocytokine levels in Kawasaki syndrome. (2008)
  • 著者名/発表者名: Kemmotsu Y, et al
  • 学会等名: Ninth International Kawasaki Disease Symposium.
  • 発表場所: Taipei, Taiwan
• [学会発表] Adiponeotin stimulates prostaglandin E_2 production from rheumatoid synovial fibroblasts. (2008)
  • 著者名/発表者名: Kusunoki K, et al
  • 学会等名: MEDICAL-EXPO 2008 in APLAR' s World. 13TH Congress of the Asia Pacific League of Associations for Rheumatology.
  • 発表場所: Yokohama, Japan
• [学会発表] Adiponectin induces interleukin-8 production from rheumatoid synovial fibroblasts. (2008)
  • 著者名/発表者名: Kitahara K, et al
  • 学会等名: MEDICAL-EXPO 2008 in APLAR' s World. 13TH Congress of the Asia Pacific League of Associations for Rheumatology.
  • 発表場所: Yokohama, Japan
• [学会発表] History and Recent Advance in NSAID. (2008)
  • 著者名/発表者名: Kawai S, et al
  • 学会等名: MEDICAL-EXPO 2008 in APLAR' s World. 13TH Congress of the Asia Pacific League of Associations for Rheumatology.
  • 発表場所: Yokohama, Japan
• [学会発表] Elevated serum leptin and adiponectin levels, but decreased resistin level in systemic lupus erytematousus. (2008)
  • 著者名/発表者名: Tanaka-Matsumoto Nahoko, et al
  • 学会等名: 72nd. American College of Rheumatology Annual Scientific Meeting.
  • 発表場所: San Francisco, USA
• [図書] ササッとわかる最新「関節リウマチ」治療法 (2008)
  • 著者名/発表者名: 川合眞一 著
  • 総ページ数: 110
  • 出版者: 講談社
• [備考] ホームページ等
  • URL: http://www.lab.toho-u.ac.jp/med/omori/kogen/research/achievement.html
• [備考]
  • URL: http://www.lab.toho-u.ac.jp/med/omori/kogen/research/achievement.html
• [備考]
  • URL: http://www.lab.toho-u.ac.jp/med/omori/kogen/research/achievement.html