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Anti‐TNFα (Remicade®) therapy protects dystrophic skeletal muscle from necrosis
Author(s) -
Grounds Miranda D.,
Torrisi Jo
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-1024com
Subject(s) - dystrophin , duchenne muscular dystrophy , skeletal muscle , tumor necrosis factor alpha , muscular dystrophy , necrosis , myocyte , myopathy , inflammation , medicine , mdx mouse , endocrinology
Necrosis of skeletal muscle fibers in the lethal childhood myopathy Duchenne muscular dystrophy (DMD) results from defects in the cell membrane‐associated protein dystrophin. This study tests the novel hypothesis that the initial sarcolemmal breakdown resulting from dystrophin deficiency is exacerbated by inflammatory cells and that cytokines specifically tumor necrosis factor‐ α (TNF α ) contribute to muscle necrosis. To block in vivo TNF α bioactivity young dystrophic mdx mice (a model for DMD) were injected weekly from 7 days of age with the anti‐TNF α antibody Remicade® before the onset of muscle necrosis and dystropathology that normally occurs at 21 days postnatally. The extent of inflammation muscle necrosis and myotube formation was measured by histological analysis from 18 to 28 days and muscle damage was also visualized by penetration of Evans blue dye into myofibers. Data from Remicade ‐treated and control mdx mice were compared with mdx/TNF α (−/−) mice that lack TNF α . Pharmacological blockade of TNF α activity with Remicade® clearly delayed and greatly reduced the breakdown of dystrophic muscle in marked contrast to the situation in mdx and mdx/ TNF α (−/−) mice. Remicade had no adverse effect on new muscle formation. Remicade is a highly specific anti‐inflammatory intervention and clinical application to muscular dystrophies is suggested by this marked protective effect against skeletal muscle breakdown.—Grounds M. D. Torrisi J. Anti‐TNF α (Remicade) therapy protects dystrophic skeletal muscle from necrosis.