Reduced muscle necrosis and long-term benefits in dystrophic mdx mice after cV1q (blockade of TNF) treatment

Neuromuscul Disord. 2008 Mar;18(3):227-38. doi: 10.1016/j.nmd.2007.11.002. Epub 2008 Jan 22.

Abstract

Tumour necrosis factor (TNF) is a potent inflammatory cytokine that appears to exacerbate damage of dystrophic muscle in vivo. The monoclonal murine specific antibody cV1q that specifically neutralises murine TNF demonstrated significant anti-inflammatory effects in dystrophic mdx mice. cV1q administration protected dystrophic skeletal myofibres against necrosis in both young and adult mdx mice and in adult mdx mice subjected to 48 h voluntary wheel exercise. Long-term studies (up to 90 days) in voluntarily exercised mdx mice showed beneficial effects of cV1q treatment with reduced histological evidence of myofibre damage and a striking decrease in serum creatine kinase levels. However, in the absence of exercise long-term cV1q treatment did not reduce necrosis or background pathology in mdx mice. An additional measure of well-being in the cV1q treated mice was that they ran significantly more than control mdx mice.

MeSH terms

  • Age Factors
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Disease Models, Animal
  • Female
  • Immunotherapy
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / physiology
  • Muscular Dystrophy, Animal / drug therapy*
  • Muscular Dystrophy, Animal / pathology*
  • Muscular Dystrophy, Animal / physiopathology
  • Muscular Dystrophy, Duchenne / drug therapy
  • Muscular Dystrophy, Duchenne / pathology
  • Muscular Dystrophy, Duchenne / physiopathology
  • Myofibrils / pathology
  • Necrosis
  • Physical Conditioning, Animal
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha