SEARCH:   Advanced

Blood, 15 October 2005, Vol. 106, No. 8, pp. 2627-2632. Prepublished online as a Blood First Edition Paper on July 5, 2005; DOI 10.1182/blood-2004-12-4602. This Article Full Text (PDF) All Versions of this Article: 2004-12-4602v1 106/8/2627    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nishimoto, N. Articles by Kishimoto, T. Search for Related Content PubMed PubMed Citation Articles by Nishimoto, N. Articles by Kishimoto, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 2, 2004 Accepted June 12, 2005 Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman's disease Norihiro Nishimoto*, Yuzuru Kanakura, Katsuyuki Aozasa, Takeshi Johkoh, Minoru Nakamura, Shuji Nakano, Nobuaki Nakano, Yasuo Ikeda, Takeshi Sasaki, Kiyoshi Nishioka, Masamichi Hara, Hirokuni Taguchi, Yukihiko Kimura, Yoshiro Kato, Hideki Asaoku, Shunichi Kumagai, Fumio Kodama, Hideko Nakahara, Keisuke Hagihara, Kazuyuki Yoshizaki, and Tadamitsu Kishimoto Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan Department of Hematology and Oncology, Osaka University, Suita, Osaka, Japan Department of Pathology, Osaka University, Suita, Osaka, Japan Department of Medical Physics, Osaka University, Suita, Osaka, Japan First Department of Internal Medicine, Kyushu University, Fukuoka, Japan Department of Internal Medicine, Kyowakai Hospital, Suita, Osaka, Japan Department of Internal Medicine, Keio University School of Medicine, Shinjukuku, Tokyo, Japan Department of Rheumatology and Hematology, Tohoku University, Sendai, Miyagi, Japan Department of Dermatology, Tokyo Medical and Dental University, Bunkyouku, Tokyo, Japan Department of Internal Medicine, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan Third Department of Internal Medicine, Kochi Medical School, Nangoku, Kochi, Japan First Department of Internal Medicine, Tokyo Medical University, Shinjukuku, Tokyo, Japan Department of Hematology, Aichi Medical University, Nagakutecho, Aichi, Japan Fourth Department of Internal Medicine, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan Department of Biomedical Infomatics, Kobe University, Kobe, Hyogo, Japan Department of Chemotherapy, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan Department of Medical Science I, School of Health and Sport Sciences, Osaka University, Suita, Osaka, Japan * Corresponding author; email: norihiro{at}fbs.osaka-u.ac.jp. Multicentric Castleman's disease (MCD) is an atypical lymphoproliferative disorder characterized by systemic lymphadenopathy and constitutional inflammatory symptoms. Dysregulated overproduction of interleukin-6 is responsible for the clinical abnormalities. This multicenter prospective study was undertaken to evaluate the safety and efficacy of a humanized anti-human-IL-6 receptor monoclonal antibody (MRA) in patients with MCD. We report here the first 60-week results of the study enrolling 28 patients. The initial dosing period consisted of 8 infusions of 8mg/kg MRA administered biweekly. Adjustments in the dose and treatment interval were allowed for each patient in an extension phase after 16 weeks. Within 16 weeks, treatment with MRA consistently improved lymphadenopathy and all the inflammatory parameters. Hemoglobin, albumin, total cholesterol and high-density lipoprotein cholesterol values, and body-mass-index, all increased significantly. Fatigue also improved. Chronic inflammatory symptoms were successfully managed over 60 weeks. In eight patients (28.6%), the MRA dose was decreased or the treatment interval was extended without exacerbation. Eleven out of 15 patients (73.3%) who had received oral corticosteroids prior to study entry were able to reduce the corticosteroid dose. Most adverse events were mild to moderate in severity. MRA was well tolerated and significantly improved chronic inflammatory symptoms and wasting in the MCD patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Kurosawa, N. Akiyama, A. Ohwada, M. Warabi, M. Suenaga, M. Kojima, and J. Tomiyama Idiopathic Plasmacytic Lymphadenopathy with Polyclonal Hypergammaglobulinemia Accompanied with Cutaneous Involvement and Renal Dysfunction Jpn. J. Clin. Oncol., October 1, 2009; 39(10): 682 - 685. [Abstract] [Full Text] [PDF] S. Shinriki, H. Jono, K. Ota, M. Ueda, M. Kudo, T. Ota, Y. Oike, M. Endo, M. Ibusuki, A. Hiraki, et al. Humanized Anti-Interleukin-6 Receptor Antibody Suppresses Tumor Angiogenesis and In vivo Growth of Human Oral Squamous Cell Carcinoma Clin. Cancer Res., September 1, 2009; 15(17): 5426 - 5434. [Abstract] [Full Text] [PDF] A. Morishima, A. Marui, T. Shimamoto, Y. Saji, T. Nishina, and M. Komeda A case of interleukin-6-producing cardiac myxoma resembling multicentric Castleman's disease. J. Thorac. Cardiovasc. Surg., August 1, 2009; 138(2): 499 - 501. [Full Text] [PDF] M. A. Nowell, A. S. Williams, S. A. Carty, J. Scheller, A. J. Hayes, G. W. Jones, P. J. Richards, S. Slinn, M. Ernst, B. J. Jenkins, et al. Therapeutic Targeting of IL-6 Trans Signaling Counteracts STAT3 Control of Experimental Inflammatory Arthritis J. Immunol., January 1, 2009; 182(1): 613 - 622. [Abstract] [Full Text] [PDF] H. Komaba, T. Nakazawa, Y. Yamaguchi, S. Kumagai, and M. Fukagawa Interleukin-6 receptor inhibition with tocilizumab in various renal involvements associated with multicentric Castleman's disease: a report of three cases NDT Plus, December 1, 2008; 1(6): 423 - 426. [Abstract] [Full Text] [PDF] N. Nishimoto, K. Terao, T. Mima, H. Nakahara, N. Takagi, and T. Kakehi Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease Blood, November 15, 2008; 112(10): 3959 - 3964. [Abstract] [Full Text] [PDF] T. Nishikawa, K. Hagihara, S. Serada, T. Isobe, A. Matsumura, J. Song, T. Tanaka, I. Kawase, T. Naka, and K. Yoshizaki Transcriptional Complex Formation of c-Fos, STAT3, and Hepatocyte NF-1{alpha} Is Essential for Cytokine-Driven C-Reactive Protein Gene Expression J. Immunol., March 1, 2008; 180(5): 3492 - 3501. [Abstract] [Full Text] [PDF] B. Rabe, A. Chalaris, U. May, G. H. Waetzig, D. Seegert, A. S. Williams, S. A. Jones, S. Rose-John, and J. Scheller Transgenic blockade of interleukin 6 transsignaling abrogates inflammation Blood, February 1, 2008; 111(3): 1021 - 1028. [Abstract] [Full Text] [PDF] B. Ahmed, J. A. Tschen, P. R. Cohen, M. H. Zaki, P. L. Rady, S. K. Tyring, R. E. Corringham, and R. Kurzrock Cutaneous castleman's disease responds to anti interleukin-6 treatment Mol. Cancer Ther., September 1, 2007; 6(9): 2386 - 2390. [Abstract] [Full Text] [PDF] N. Nishimoto, J. Hashimoto, N. Miyasaka, K. Yamamoto, S. Kawai, T. Takeuchi, N. Murata, D. van der Heijde, and T. Kishimoto Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab Ann Rheum Dis, September 1, 2007; 66(9): 1162 - 1167. [Abstract] [Full Text] [PDF] H. Kawabata, N. Tomosugi, J. Kanda, Y. Tanaka, K. Yoshizaki, and T. Uchiyama Anti-interleukin 6 receptor antibody tocilizumab reduces the level of serum hepcidin in patients with multicentric Castleman's disease Haematologica, June 1, 2007; 92(6): 857 - 858. [Abstract] [Full Text] [PDF] K. Izumi-Nagai, N. Nagai, Y. Ozawa, M. Mihara, Y. Ohsugi, T. Kurihara, T. Koto, S. Satofuka, M. Inoue, K. Tsubota, et al. Interleukin-6 Receptor-Mediated Activation of Signal Transducer and Activator of Transcription-3 (STAT3) Promotes Choroidal Neovascularization Am. J. Pathol., June 1, 2007; 170(6): 2149 - 2158. [Abstract] [Full Text] [PDF] J. L. Ryan, J. K. Carroll, E. P. Ryan, K. M. Mustian, K. Fiscella, and G. R. Morrow Mechanisms of Cancer-Related Fatigue Oncologist, May 1, 2007; 12(suppl_1): 22 - 34. [Abstract] [Full Text] [PDF] C.-F. Qi, J. X. Zhou, C. H. Lee, Z. Naghashfar, S. Xiang, A. L. Kovalchuk, T. N. Fredrickson, J. W. Hartley, D. C. Roopenian, W. F. Davidson, et al. Anaplastic, Plasmablastic, and Plasmacytic Plasmacytomas of Mice: Relationships to Human Plasma Cell Neoplasms and Late-Stage Differentiation of Normal B Cells Cancer Res., March 15, 2007; 67(6): 2439 - 2447. [Abstract] [Full Text] [PDF] S. Metz, M. Wiesinger, M. Vogt, H. Lauks, G. Schmalzing, P. C. Heinrich, and G. Muller-Newen Characterization of the Interleukin (IL)-6 Inhibitor IL-6-RFP: FUSED RECEPTOR DOMAINS ACT AS HIGH AFFINITY CYTOKINE-BINDING PROTEINS J. Biol. Chem., January 12, 2007; 282(2): 1238 - 1248. [Abstract] [Full Text] [PDF] S. Rose-John, J. Scheller, G. Elson, and S. A. Jones Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer J. Leukoc. Biol., August 1, 2006; 80(2): 227 - 236. [Abstract] [Full Text] [PDF] M. Maggio, J. M. Guralnik, D. L. Longo, and L. Ferrucci Interleukin-6 in aging and chronic disease: a magnificent pathway. J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2006; 61(6): 575 - 584. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020