Suppression of experimental myasthenia gravis, a B cell-mediated autoimmune disease, by blockade of IL-18

Sin Hyeog Im, Dora Barchan, Prasanta Kumar Maiti, Lily Raveh, Miriam C. Souroujon, Sara Fuchs

Research output: Contribution to journalArticlepeer-review


Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine that plays an important role in interferon gamma (IFN-γ) production and IL-12-driven Th1 phenotype polarization. Increased expression of IL-18 has been observed in several autoimmune diseases. In this study we have analyzed the role of IL-18 in an antibody-mediated autoimmune disease and elucidated the mechanisms involved in disease suppression mediated by blockade of IL-18, using experimental autoimmune myasthenia gravis (EAMG) as a model. EAMG is a T cell-regulated, antibody-mediated autoimmune disease in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. Th1- and Th2-type responses are both implicated in EAMG development. We show that treatment by anti-IL-18 during ongoing EAMG suppresses disease progression. The protective effect can be adoptively transferred to naive recipients and is mediated by increased levels of the immunosuppressive Th3-type cytokine TGF-β and decreased AChR-specific Th1-type cellular responses. Suppression of EAMG is accompanied by down-regulation of the costimulatory factor CD40L and up-regulation of CTLA-4, a key negative immunomodulator. Our results suggest that IL-18 blockade may potentially be applied for immunointervention in myasthenia gravis.

Original languageEnglish
Pages (from-to)2140-2148
Number of pages9
JournalFASEB Journal
Issue number12
StatePublished - 2001
Externally publishedYes


  • Autoimmunity
  • Cytokines and costimulatory factors
  • Immunotherapy
  • Interleukin 18
  • MG


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