IFN-alpha therapy is effective in suppressing the clinical experimental myasthenia gravis.
To study the therapeutic efficacy of IFN-alpha after the onset of clinical signs of experimental autoimmune myasthenia gravis (EAMG), we treated mice with clinical EAMG with recombinant human IFN-alpha or mouse IFN-alpha. In the first experiment, 7 of 16 (44%) mice had a complete clinical remission in the recombinant human IFN-alpha-treated group, in contrast to none in the placebo group (0/14) (p = 0.006). There was a higher incidence of death and severe disease in the placebo group (7/14) relative to the IFN-alpha group (4/16). In the second experiment, 6 of 18 (33%) mice in the mouse IFN-alpha-treated group had a complete clinical remission, while none of 17 (0%) mice in the placebo-treated group had remission (p = 0.011). Again, more mice died or worsened in the placebo group (11/17) compared with the IFN-alpha group (7/18). IFN-alpha treatment significantly reduced the anti-acetylcholine receptor (AChR) Ab levels, especially the IgG1 and IgG2b isotypes, and the amount of anti-AChR Abs bound to muscle AChR. IFN-alpha treatment also lowered CD4 cells in the lymph nodes and spleen, and suppressed the in vitro lymphocyte proliferative response to AChR and its dominant peptide in a dose-dependent manner.
Deng
C
C
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, 77555, USA.
Goluszko
E
E
Baron
S
S
Wu
B
B
Christadoss
P
P
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007370:Interferon Type I / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000276:immunology; D009157:Myasthenia Gravis / Q000188:drug therapy*; D011978:Receptors, Nicotinic / Q000276:immunology; D011994:Recombinant Proteins
D001323:Autoantibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D016056:Immunodominant Epitopes; D007132:Immunoglobulin Isotypes; D007370:Interferon Type I; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins