Physiological effects of modulating the interleukin-6 axis

被引：97
作者：
Schett, Georg [1 ,2 ]
机构：
[1] Friedrich Alexander Univ Erlangen Nurnberg FAU, Dept Internal Med Rheumatol & Immunol 3, Erlangen, Germany
[2] Univ Klinikum Erlangen, Erlangen, Germany
来源：
RHEUMATOLOGY | 2018年 / 57卷
关键词：
giant cell arteritis; interleukin; 6; tocilizumab; vasculitis; cytokines; GIANT-CELL ARTERITIS; RECEPTOR ANTIBODY TOCILIZUMAB; RHEUMATOID-ARTHRITIS PATIENTS; PITUITARY-ADRENAL AXIS; ACUTE PHASE PROTEINS; SOLUBLE INTERLEUKIN-6; POLYMYALGIA-RHEUMATICA; DISEASE-ACTIVITY; TNF-ALPHA; HEPATIC INFLAMMATION;
D O I：
10.1093/rheumatology/kex513
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
IL-6 is a pleiotropic cytokine involved in many biological functions that affect tissues beyond the immune system and the vasculature. This multifunctional cytokine exerts its actions via the classic signalling pathway when it binds to the transmembrane IL-6 receptor (IL-6R) or via the trans-signalling pathway upon binding to the soluble form of IL-6R (sIL-6R). In general, classic IL-6 signalling is responsible for the anti-inflammatory properties of IL-6, whereas trans-signalling is responsible for the pro-inflammatory actions of IL-6. As a result, dysregulation of the IL-6 axis can lead to the onset or development of several disease states, particularly autoimmune and inflammatory disorders, including RA and GCA. This pathological role of IL-6 means that pharmacologic modulation of the IL-6 axis is a rational therapeutic approach; however, multiple predictable, but often underappreciated, effects on tissues and organs beyond the blood vessels may also occur.
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收藏
页码：43 / 50
页数：8
相关论文
共 106 条
[1]   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
[2]  
[Anonymous], 2017, ACT TOC PACK INS
[3]  
[Anonymous], INT J RHEUMATOL
[4]   Correlations between immunogenicity, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab [J].
Benucci, Maurizio ;
Meacci, Francesca ;
Grossi, Valentina ;
Infantino, Maria ;
Manfredi, Mariangela ;
Bellio, Emanuele ;
Bellio, Valerio ;
Li Gobbi, Francesca ;
Bazzichi, Laura ;
Moscato, Paolo ;
Caputo, Dario ;
Saviola, Gianantonio ;
Talotta, Rossella ;
Sarzi-Puttini, Piercarlo ;
Atzeni, Fabiola .
BIOLOGICS-TARGETS & THERAPY, 2016, 10 :53-58
[5]   Anti-interleukin 6 receptor therapy as rescue treatment for giant cell arteritis [J].
Beyer, Christian ;
Axmann, Roland ;
Sahinbegovic, Enijad ;
Distler, Joerg H. ;
Manger, Bernhard ;
Schett, Georg ;
Zwerina, Jochen .
ANNALS OF THE RHEUMATIC DISEASES, 2011, 70 (10) :1874-1875
[6]   IL-6 biology: implications for clinical targeting in rheumatic disease [J].
Calabrese, Leonard H. ;
Rose-John, Stefan .
NATURE REVIEWS RHEUMATOLOGY, 2014, 10 (12) :720-727
[7]   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
[8]   IL-6 switches the differentiation of monocytes from dendritic cells to macrophages [J].
Chomarat, P ;
Banchereau, J ;
Davoust, J ;
Palucka, AK .
NATURE IMMUNOLOGY, 2000, 1 (06) :510-514
[9]   SEMINARS IN MEDICINE OF THE BETH-ISRAEL-HOSPITAL, BOSTON - THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND IMMUNE-MEDIATED INFLAMMATION [J].
CHROUSOS, GP .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (20) :1351-1362
[10]   Inhibition of T cell apoptosis in the aqueous humor of patients with uveitis by IL-6/soluble IL-6 receptor trans-signaling [J].
Curnow, SJ ;
Scheel-Toellner, D ;
Jenkinson, W ;
Raza, K ;
Durrani, OM ;
Faint, JM ;
Rauz, S ;
Wloka, K ;
Pilling, D ;
Rose-John, S ;
Buckley, CD ;
Murray, PI ;
Salmon, M .
JOURNAL OF IMMUNOLOGY, 2004, 173 (08) :5290-5297
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