Production of IL-6 by human myoblasts stimulated with Aβ: Relevance in the pathogenesis of IBM

Objective: To determine whether amyloid-β protein (Aβ) can induce the production of proinflammatory cytokines by cultured normal muscle cells. Background: Sporadic inclusion body myositis (IBM) is characterized by the presence of rimmed vacuoles and fibrillary inclusions of Aβ in muscle fibers, and often inflammatory cells. Endomysial expression of proinflammatory molecules has suggested an ongoing immune process, but the site of sensitization and the mechanisms that trigger an inflammatory reaction is unknown. Methods: The authors used Northern blot analysis and specific immunoassays to study the expression and secretion in cell-free supernatants of tumor necrosis factor-α (TNFα), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by purified human myoblasts and C2C12 mouse skeletal muscle cells incubated with Aβ[1-42] or Aβ[25-35] peptides. Results: Nonstimulated muscle cells produced detectable IL-6, whereas secretion of IL-1β and TNFα was absent. Incubation with Aβ peptides increased IL-6 production, whereas TNFα and IL-1β levels remained undetectable. Northern blot analysis of Aβ-stimulated human myoblasts revealed an increase in IL-6 mRNA expression. Conclusions: Cultured muscle cells increase the constitutive production of IL-6 in response to local deposition of Aβ in sporadic IBM. IL-6 could be a CD8⁺ proliferation and differentiation agent, an autocrine proteolysis-inducing factor of damaged myotubes, and a proliferation-stimulating agent for satellite cells to replace the destroyed myofibers in IBM.