Anti-TNF-α antibodies suppress the development of experimental autoimmune myasthenia gravis

被引:57
作者
Duan, RS
Wang, HB
Yang, JS
Scallon, B
Link, H
Xiao, BG [1 ]
机构
[1] Huddinge Univ Hosp, Karolinska Inst, Div Neurol, Expt Neurol & Neuroimmunol Unit, S-14186 Huddinge, Sweden
[2] Shandong Qianfoshan Hosp, Div Neurol, Shandong, Peoples R China
[3] Centocor Inc, Malvern, PA USA
关键词
experimental autoimmune myasthenia gravis; anti-TNF-alpha antibodies; cytokine; anti-AChR antibodies;
D O I
10.1006/jaut.2002.0618
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To understand the role of TNF-alpha in the induction of experimental autoimmune myasthenia gravis (EAMG) and detect a possible effect of anti-TNF-alpha antibodies in the treatment of EAMG, anti-TNF-a antibodies were administrated intraperitoneally to Lewis rats twice per week for 5 weeks from the day of immunization with Torpedo AChR and complete Freund's adjuvant (CFA). Administration of anti-TNF-a antibodies resulted in lower incidence of EAMG, and in delayed onset and only mild muscle weakness compared with control EAMG rats. These mild clinical signs were accompanied by lower AChR-specific lymphocyte proliferation, down-regulated IFN-gamma and IL-10, and up-regulated TGF-beta. The lower levels of anti-AChR IgG, Ig2a and lgG2b and decreased anti-AChR IgG affinity were found in rats treated with anti-TNF-a antibodies. These results demonstrate that anti-TNF-a antibodies can suppress the induction and development of EAMG. (C) 2002 Published by Elsevier Science Ltd.
引用
收藏
页码:169 / 174
页数:6
相关论文
共 32 条
[1]   MEDICAL PROGRESS - MYASTHENIA-GRAVIS [J].
DRACHMAN, DB .
NEW ENGLAND JOURNAL OF MEDICINE, 1994, 330 (25) :1797-1810
[2]  
Feldmann M, 1999, ANN RHEUM DIS, V58, P27
[3]  
GRAUS YMF, 1993, CLIN EXP IMMUNOL, V92, P506
[4]   Altered immune responses in interleukin 10 transgenic mice [J].
Hagenbaugh, A ;
Sharma, S ;
Dubinett, SM ;
Wei, SHY ;
Aranda, R ;
Cheroutre, H ;
Fowell, DJ ;
Binder, S ;
Tsao, B ;
Locksley, RM ;
Moore, KW ;
Kronenberg, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (12) :2101-2110
[5]  
Harriman G, 1999, ANN RHEUM DIS, V58, P61
[6]   BIOLOGICAL PROPERTIES OF INTERLEUKIN-10 [J].
HOWARD, M ;
OGARRA, A .
IMMUNOLOGY TODAY, 1992, 13 (06) :198-200
[7]  
Huang YM, 1999, CLIN EXP IMMUNOL, V118, P304
[8]   Suppression of experimental myasthenia gravis, a B cell-mediated autoimmune disease, by blockade of IL-18 [J].
Im, SH ;
Barchan, D ;
Maiti, PK ;
Raveh, L ;
Souroujon, MC ;
Fuchs, S .
FASEB JOURNAL, 2001, 15 (12) :2140-2148
[9]  
JELINEK DF, 1987, J IMMUNOL, V139, P2970
[10]   Tumor necrosis factor blockade in actively induced experimental autoimmune encephalomyelitis prevents clinical disease despite activated T cell infiltration to the central nervous system [J].
Korner, H ;
Lemckert, FA ;
Chaudhri, G ;
Etteldorf, S ;
Sedgwick, JD .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (08) :1973-1981