Pro-inflammatory cytokines in rheumatoid arthritis

被引:69
作者
Smolen, JS [1 ]
Redlich, K [1 ]
Zwerina, J [1 ]
Aletaha, D [1 ]
Steiner, G [1 ]
Schett, G [1 ]
机构
[1] Med Univ Vienna, Div Rheumatol, Vienna, Austria
关键词
rheumatoid arthritis; cytokines; TNF; IL-1; IL-6; disease activity; joint damage; osteoclasts; therapy; anti-TNF; IL-1ra; anti-IL-6R (tocilizumab);
D O I
10.1385/CRIAI:28:3:239
中图分类号
R392 [医学免疫学];
学科分类号
100102 [免疫学];
摘要
Therapy of rheumatoid arthritis (RA) aims at interfering with the disease process, namely inflammation and destruction of the joints, and thus at preventing long-term disability. Proinflammatory cytokines play a decisive role in the generation of the inflammatory and destructive response. Aside from traditional disease-modifying anti-rheumatic drugs and tumor necrosis factor-blocking agents, a number of targeted therapies are currently in evaluation, such As abatacept (interfering with co-stimulation), rituximab (an anti-B-cell agent) and tocilizumab (an anti-interleukin-6 receptor antibody). In phase II trials, all these agents have clinical improvement, and phase III trials have been partly completed resulted in significant with similar results and are partly on the way. Because none of these agents lead to good clinical responses in all patients and many patients have only relatively low degrees of response, it will still be a challenge to find the best therapeutic paths to combat the "inflammatory house of cards" of RA.
引用
收藏
页码:239 / 248
页数:10
相关论文
共 79 条
[1]
Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage [J].
Abramson, SB ;
Amin, A .
RHEUMATOLOGY, 2002, 41 (09) :972-980
[2]
Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor [J].
AbuAmer, Y ;
Ross, FP ;
Edwards, J ;
Teitelbaum, SL .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (06) :1557-1565
[3]
Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score [J].
Aletaha, D ;
Nell, VP ;
Stamm, T ;
Uffmann, M ;
Pflugbeil, S ;
Machold, K ;
Smolen, JS .
ARTHRITIS RESEARCH & THERAPY, 2005, 7 (04) :R796-R806
[4]
A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis [J].
Bathon, JM ;
Martin, RW ;
Fleischmann, RM ;
Tesser, JR ;
Schiff, MH ;
Keystone, EC ;
Genovese, MC ;
Wasko, MC ;
Moreland, LW ;
Weaver, AL ;
Markenson, J ;
Finck, BK .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (22) :1586-1593
[5]
BRENNAN FM, 1989, LANCET, V2, P244
[6]
Bresnihan B, 1998, ARTHRITIS RHEUM, V41, P2196, DOI 10.1002/1529-0131(199812)41:12<2196::AID-ART15>3.0.CO
[7]
2-2
[8]
THE INHIBITORY ACTIVITY OF HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST IS ENHANCED BY TYPE-II INTERLEUKIN-1 SOLUBLE RECEPTOR AND HINDERED BY TYPE-I INTERLEUKIN-1 SOLUBLE RECEPTOR [J].
BURGER, D ;
CHICHEPORTICHE, R ;
GIRI, JG ;
DAYER, JM .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (01) :38-41
[9]
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
[10]
Combination of infliximab and methotrexate therapy for early rheumatoid arthritis - A randomized, controlled trial [J].
Clair, EWS ;
van der Heijde, DMFM ;
Smolen, JS ;
Maini, RN ;
Bathon, JM ;
Emery, P ;
Keystone, E ;
Schiff, M ;
Kalden, JR ;
Wang, B ;
DeWoody, K ;
Weiss, R ;
Baker, D .
ARTHRITIS AND RHEUMATISM, 2004, 50 (11) :3432-3443