Interieukin-6 in rheumatoid arthritis

被引:133
作者
Nishimoto, Norihiro [1 ]
机构
[1] Osaka Univ, Grad Sch Frontier Biosci, Lab Immune Regulat, Suita, Osaka 5650871, Japan
关键词
anticytokine therapy; Castleman's disease; interleukin-6; rheumatoid arthritis; tocilizumab;
D O I
10.1097/01.bor.0000218949.19860.d1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of review Recent progress in cytokine studies has clarified,the pathological roles played by cytokines and provided key, evidence that antagonizing their actions can be therapeutic. The. pathogenesis of rheumatoid arthritis, an autoimmune inflammatory disease, involves inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-1 and interleukin-6. Anti-tumour necrosis factor-alpha and anti-interleukin-1 therapies have been used successfully to treat rheumatoid arthritis, but they are not consistently effective. We therefore need further therapies for this refractory disease. Interleukin-6 is another target molecule for blockade in the treatment of rheumatoid arthritis. Tocilizumab is a humanized antihuman interleukin-6 receptor monoclonal antibody designed to block the actions of interleukin-6. This review addresses the pathological significance of, interleukin-6 and the current status of anti-interleukin-6, therapy for rheumatoid arthritis. Recent findings The safety and efficacy of tocilizumab have been demonstrated in clinical trials conducted in patients I wit h rheumatoid arthritis and other autoimmune inflammatory diseases, such as juvenile idiopathic arthritis and Crohn's disease. Summary Clinical studies have demonstrated the pathological significance of interleukin-6 and the safety and efficacy of anti-interleukin-6 therapy with tocilizumab., Blockade of inter leukin-6 - the second generation of anticytokine therapy - may be a promising treatment for rheumatoid arthritis.
引用
收藏
页码:277 / 281
页数:5
相关论文
共 34 条
[1]   INTERLEUKIN-6 IN BIOLOGY AND MEDICINE [J].
AKIRA, S ;
TAGA, T ;
KISHIMOTO, T .
ADVANCES IN IMMUNOLOGY, VOL 54, 1993, 54 :1-78
[2]   Interleukin 6 is required for the development of collagen-induced arthritis [J].
Alonzi, T ;
Fattori, E ;
Lazzaro, D ;
Costa, P ;
Probert, L ;
Kollias, G ;
De Benedetti, F ;
Poli, V ;
Ciliberto, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (04) :461-468
[3]   A point mutation of Tyr-759 in interleukin 6 family cytokine receptor subunit gp130 causes autoimmune arthritis [J].
Atsumi, T ;
Ishihara, K ;
Kamimura, D ;
Ikushima, H ;
Ohtani, T ;
Hirota, S ;
Kobayashi, H ;
Park, SJ ;
Saeki, Y ;
Kitamura, Y ;
Hirano, T .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (07) :979-990
[4]   RECOMBINANT HUMAN INTERLEUKIN-6 (IL-6/BSF-2/HSF) REGULATES THE SYNTHESIS OF ACUTE PHASE PROTEINS IN HUMAN HEPATOCYTES [J].
CASTELL, JV ;
GOMEZLECHON, MJ ;
DAVID, M ;
HIRANO, T ;
KISHIMOTO, T ;
HEINRICH, PC .
FEBS LETTERS, 1988, 232 (02) :347-350
[5]   Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis - A randomized, double-blind, placebo-controlled, dose-escalation trial [J].
Choy, EHS ;
Isenberg, DA ;
Garrood, T ;
Farrow, S ;
Ioannou, Y ;
Bird, H ;
Cheung, N ;
Williams, B ;
Hazleman, B ;
Price, R ;
Yoshizaki, K ;
Nishimoto, N ;
Kishimoto, T ;
Panayi, GS .
ARTHRITIS AND RHEUMATISM, 2002, 46 (12) :3143-3150
[6]   PHENOTYPIC ANALYSIS OF SYNOVIAL TISSUE AND PERIPHERAL-BLOOD LYMPHOCYTES ISOLATED FROM PATIENTS WITH RHEUMATOID-ARTHRITIS [J].
CUSH, JJ ;
LIPSKY, PE .
ARTHRITIS AND RHEUMATISM, 1988, 31 (10) :1230-1238
[7]   Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis - A large, international, multicenter, placebo-controlled trial [J].
Fleischmann, RM ;
Schechtman, J ;
Bennett, R ;
Handel, ML ;
Burmester, GR ;
Tesser, J ;
Modafferi, D ;
Poulakos, J ;
Sun, G .
ARTHRITIS AND RHEUMATISM, 2003, 48 (04) :927-934
[9]   Distinct contribution of IL-6, TNF-α, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice [J].
Hata, H ;
Sakaguchi, N ;
Yoshitomi, H ;
Iwakura, Y ;
Sekikawa, K ;
Azuma, Y ;
Kanai, C ;
Moriizumi, E ;
Nomura, T ;
Nakamura, T ;
Sakaguchi, S .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (04) :582-588
[10]   EXCESSIVE PRODUCTION OF INTERLEUKIN-6/B CELL STIMULATORY FACTOR-II IN RHEUMATOID-ARTHRITIS [J].
HIRANO, T ;
MATSUDA, T ;
TURNER, M ;
MIYASAKA, N ;
BUCHAN, G ;
TANG, B ;
SATO, K ;
SHIMIZU, M ;
MAINI, R ;
FELDMAN, M ;
KISHIMOTO, T .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1988, 18 (11) :1797-1801