Blockade of TNF in vivo using cV1q antibody reduces contractile dysfunction of skeletal muscle in response to eccentric exercise in dystrophic mdx and normal mice.
This study evaluated the contribution of the pro-inflammatory cytokine, tumour necrosis factor (TNF) to the severity of exercise-induced muscle damage and subsequent myofibre necrosis in mdx mice. Adult mdx and non-dystrophic C57 mice were treated with the mouse-specific TNF antibody cV1q before undergoing a damaging eccentric contraction protocol performed in vivo on a custom built mouse dynamometer. Muscle damage was quantified by (i) contractile dysfunction (initial torque deficit) immediately after the protocol, (ii) subsequent myofibre necrosis 48 h later. Blockade of TNF using cV1q significantly reduced contractile dysfunction in mdx and C57 mice compared with mice injected with the negative control antibody (cVaM) and un-treated mice. Furthermore, cV1q treatment significantly reduced myofibre necrosis in mdx mice. This in vivo evidence that cV1q reduces the TNF-mediated adverse response to exercise-induced muscle damage supports the use of targeted anti-TNF treatments to reduce the severity of the functional deficit and dystropathology in DMD.
School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Crawley, WA 6009, Australia.
A T
AT
Piers
T
T
Lavin
H G
HG
Radley-Crabb
A J
AJ
Bakker
M D
MD
Grounds
G J
GJ
Pinniger
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D053581:Muscle Strength Dynamometer; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology / Q000503:physiopathology*; D009336:Necrosis; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012508:Sarcolemma / Q000473:pathology; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha