Altered pathological progression of diaphragm and quadriceps muscle in TNF-deficient, dystrophin-deficient mice

We have previously demonstrated a role for T cells in Duchenne muscular dys trophy (DMD) using the mdx mouse and have shown that T cell killing of dyst rophic muscle can occur through perforin-dependent and perforin-independent mechanisms. In this investigation, we explore the possibility that one per forin-independent mechanism utilized by the T cells is cytokine-based killi ng, specifically by tumor necrosis factor (TNF). We tested this hypothesis by generating mice that are TNF-deficient and dystrophin-deficient (TNF-/md x). Body mass and muscle mass of the TNF-/mdx mice were significantly less than TNF+/mdx mice at 8 weeks of age. Creatine kinase levels and overall mu scle strength were unchanged. Histopathology measurements showed different results in the diaphragm and quadriceps muscles. These data suggest that re moval of TNF in vivo in dystrophic mice has differential effects on diaphra gm and quadriceps suggesting that TNF is an unfavorable target for immunoth erapy for DMD. (C) 2000 Elsevier Science B.V. All rights reserved.