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Tumor necrosis factor- promotes the accumulation of neutrophils and macrophages in skeletal muscle

Department of Kinesiology, The University of Toledo, Toledo, Ohio

Submitted 17 November 2005 ; accepted in final form 1 July 2006

Tumor necrosis factor- (TNF-) has been associated with cachexia and is known to regulate multiple inflammatory cell (neutrophil and macrophage) responses. We tested the hypothesis that neutrophils and macrophages accumulate in the extensor digitorum longus (EDL) and soleus muscles of mice after chronic TNF- administration. Murine recombinant TNF- (100 µg·kg^–1·day^–1) in vehicle solution or vehicle solution alone (sham) was administered to C57BL/6 mice for 7 days via osmotic minipumps. In EDL muscles from TNF--treated mice, neutrophil and macrophage concentrations were elevated seven- and threefold, respectively, compared with sham mice. Neutrophil and macrophage concentrations were also elevated five- and twofold, respectively, in solei of TNF-- relative to sham-treated mice. Treatment with TNF- elevated ubiquitin content by 25% relative to sham values for both the EDL and soleus muscles; however, these elevations were not statistically significant. No differences were observed between TNF-- and sham-treated mice in body weight, food consumption, muscle mass, myofiber cross-sectional area, carbonyl groups, total protein content, or relative abundance of myosin heavy chain protein. Furthermore, no overt signs of muscle injury or regeneration were observed in muscles from TNF--treated mice in either the EDL or soleus muscles. These observations suggest that 7 days of TNF- administration promote muscle inflammation as indicated by the accumulation of neutrophils and macrophages without overt signs of atrophy, injury, or regeneration.

neutrophils; macrophages; cytokine

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