Anti-TNF-alpha antibodies suppress the development of experimental autoimmune myasthenia gravis.
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-alpha 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-alpha 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 IgG2b and decreased anti-AChR IgG affinity were found in rats treated with anti-TNF-alpha antibodies. These results demonstrate that anti-TNF-alpha antibodies can suppress the induction and development of EAMG.
Duan
Rui-Sheng
RS
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Wang
Hua-Bing
HB
Yang
Jian-She
JS
Scallon
Bernie
B
Link
Hans
H
Xiao
Bao-Guo
BG
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D011978:Receptors, Nicotinic / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014101:Torpedo / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000906:Antibodies; D011978:Receptors, Nicotinic; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma