IL-1 receptor antagonist-mediated therapeutic effect in murine myasthenia gravis is associated with suppressed serum proinflammatory cytokines, C3, and anti-acetylcholine receptor IgG1.
In myasthenia gravis (MG), TNF and IL-1beta polymorphisms and high serum levels of these proinflammatory cytokines have been observed. Likewise, TNF and IL-1beta are critical for the activation of acetylcholine receptor (AChR)-specific T and B cells and for the development of experimental autoimmune myasthenia gravis (EAMG) induced by AChR immunization. We tested the therapeutic effect of human recombinant IL-1 receptor antagonist (IL-1ra) in C57BL/6 mice with EAMG. Multiple daily injections of 0.01 mg of IL-1ra administered for 2 wk following two AChR immunizations decreased the incidence and severity of clinical EAMG. Furthermore, IL-1ra treatment of mice with ongoing clinical EAMG reduced the clinical symptoms of disease. The IL-1ra-mediated suppression of clinical disease was associated with suppressed serum IFN-gamma, TNF-alpha, IL-1beta, IL-2, IL-6, C3, and anti-AChR IgG1 without influencing total serum IgG. Therefore, IL-1ra could be used as a nonsteroidal drug for the treatment of MG.
Yang
Huan
H
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Tüzün
Erdem
E
Alagappan
Dhivyaa
D
Yu
Xiang
X
Scott
Benjamin G
BG
Ischenko
Alexander
A
Christadoss
Premkumar
P
D000818:Animals; D002478:Cells, Cultured; D003176:Complement C3 / Q000037:antagonists & inhibitors* / Q000502:physiology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000097:blood; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D021122:Protein Subunits / Q000008:administration & dosage / Q000276:immunology; D011950:Receptors, Cholinergic / Q000008:administration & dosage / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000502:physiology / Q000627:therapeutic use*; D014101:Torpedo / Q000276:immunology
D003176:Complement C3; D016207:Cytokines; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D010446:Peptide Fragments; D021122:Protein Subunits; D011950:Receptors, Cholinergic; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins