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J Appl Physiol (July 13, 2006). doi:10.1152/japplphysiol.01453.2005
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Submitted on November 16, 2005
Accepted on July 1, 2006

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

Jennifer M Peterson1, Kevin D Feeback1, Joel H Baas1, and Francis X. Pizza1*

1 Kinesiology, The University of Toledo, Toledo, Ohio, United States

* To whom correspondence should be addressed. E-mail: francis.pizza{at}utoledo.edu.

Tumor necrosis factor-alpha (TNF-{alpha}) 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-{alpha} administration. Murine recombinant TNF-{alpha} (~100 µg.kg-1.day-1) in vehicle solution or vehicle solution alone (sham) was administered to C57BL/6 mice for 7 days via mini-osmotic pumps. In EDL muscles from TNF-{alpha} treated mice, neutrophil and macrophage concentrations were elevated seven and three fold respectively, compared to sham mice. Neutrophil and macrophage concentrations were also elevated five and two fold respectively, in solei of TNF-{alpha} relative to sham treated mice. Treatment with TNF-{alpha} 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-{alpha} 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-{alpha} treated mice in either the EDL or soleus muscles. These observations suggest that TNF-{alpha} promotes muscle inflammation as indicated by the accumulation of neutrophils and macrophages without overt signs of atrophy, injury or regeneration.




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