The objective of this study was to determine the effect of anti-IL-6 receptor antibody on muscle weakness in experimental autoimmune myasthenia gravis (EAMG) mice.

Myasthenia gravis is an autoimmune disease most commonly caused by autoantibodies against neuromuscular junction molecules, such as acetylcholine receptor (AChR), and clinically characterized by fatigable muscle weakness. Preclinical and clinical data indicate that IL-6 could be a key molecule involved in pathogenesis of generalized myasthenia gravis. However, the detailed mechanism of action of IL-6 and effects of anti-IL-6 receptor (IL-6R) antibody are under investigation.

EAMG mouse model was generated by subcutaneous immunization with purified Torpedo AChR emulsified in complete Freund’s adjuvant. Four weeks after the initial immunization, mice received a booster immunization with AChR emulsified in incomplete Freund’s adjuvant. Rat anti-mouse anti-IL-6R antibody (MR16-1) was administered intraperitoneally once a week. Muscle strength was evaluated by grip test. Serum and tibialis anterior muscle were subsequently harvested for evaluation of anti-AChR antibody titer and deposition of IgG to the muscle by electrochemiluminescence immunoassay and immunohistochemistry, respectively.

In AChR-immunized EAMG mice, grip strength was significantly decreased compared to control mice. In addition, anti-AChR antibody in the sera and deposition of IgG in the tibialis anterior muscle, which was co-localized with AChR, significantly increased. Administration of MR16-1 prevented development of muscle weakness in AChR-immunized EAMG mice. Moreover, MR16-1 treatment decreased anti-AChR antibody production and deposition in the muscles.

Anti-IL-6R antibody prevented development of muscle weakness and reduced anti-AChR antibody production and deposition in AChR-immunized EAMG mice.