IL-1 receptor antagonist-mediated therapeutic effect in murine myasthenia gravis is associated with suppressed serum proinflammatory cytokines, C3, and anti-acetylcholine receptor IgG1

Huan Yang, Erdem Tüzün, Dhivyaa Alagappan, Xiang Yu, Benjamin G. Scott, Alexander Ischenko, Premkumar Christadoss

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Abstract

In myasthenia gravis (MG), TNF and IL-1β polymorphisms and high serum levels of these proinflammatory cytokines have been observed. Likewise, TNF and IL-1β 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-γ, TNF-α, IL-1β, 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.

Original languageEnglish (US)
Pages (from-to)2018-2025
Number of pages8
JournalJournal of Immunology
Volume175
Issue number3
StatePublished - Aug 1 2005

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Autoimmune Experimental Myasthenia Gravis
Interleukin-1 Receptors
Myasthenia Gravis
Cholinergic Receptors
Therapeutic Uses
Immunoglobulin G
Cytokines
Interleukin-1
Serum
Immunization
Inbred C57BL Mouse
Interleukin-2
Interleukin-6
B-Lymphocytes
T-Lymphocytes
Injections
Incidence
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology

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IL-1 receptor antagonist-mediated therapeutic effect in murine myasthenia gravis is associated with suppressed serum proinflammatory cytokines, C3, and anti-acetylcholine receptor IgG1. / Yang, Huan; Tüzün, Erdem; Alagappan, Dhivyaa; Yu, Xiang; Scott, Benjamin G.; Ischenko, Alexander; Christadoss, Premkumar.

In: Journal of Immunology, Vol. 175, No. 3, 01.08.2005, p. 2018-2025.

Research output: Contribution to journalArticle

Yang, Huan ; Tüzün, Erdem ; Alagappan, Dhivyaa ; Yu, Xiang ; Scott, Benjamin G. ; Ischenko, Alexander ; Christadoss, Premkumar. / 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: Journal of Immunology. 2005 ; Vol. 175, No. 3. pp. 2018-2025.
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AU - Alagappan, Dhivyaa

AU - Yu, Xiang

AU - Scott, Benjamin G.

AU - Ischenko, Alexander

AU - Christadoss, Premkumar

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