Macrophage migration inhibitory factor in normal human skeletal muscle and inflammatory myopathies.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine secreted by activated T cells and macrophages that has antiapoptotic, proproliferative, and chemotactic effects. Because these cells are major components of many muscle disorders with different etiologies, we investigated the amount and distribution of MIF in inflammatory myopathies. Concentrations of MIF in protein lysates from dermatomyositis (n = 6), polymyositis (n = 7), sporadic inclusion body myositis (n = 9) muscle samples and control biopsies without specific changes (n = 10) were determined by ELISA. In polymyositis, MIF concentrations were higher than in controls (p<0.05), whereas they were not significantly different in other inflammatory myopathies. By immunohistochemistry, MIF was detected not only in inflammatory cells, but also at muscle fiber membranes where they were invaded or bordered infiltrates or necrotic fibers; focal sarcoplasmic reactivity was also observed. A similar distribution was found in areas of infiltration, necrosis, myophagocytosis, degeneration, and regeneration in 8 muscular dystrophy samples. The expression of MIF was verified in human myogenic tissue cultures; MIF immunoreactivity decreased with progressive differentiation, and its distribution changed. These data suggest that MIF is a skeletal muscle cytokine with probable functions beyond inflammatory pathology in the complex regenerative response to muscle fiber damage.