Tumor Necrosis Factor-alpha Promotes Skeletal Muscle Inflammation

Abstract

Tumor necrosis factor (TNF)-alpha, a pro-inflammatory cytokine, is thought to contribute to cachexia (muscle wasting) and promote skeletal muscle inflammation. PURPOSE To determine if TNF-alpha administration promotes the accumulation of inflammatory cells in skeletal muscle. METHODS: Murine recombinant TNF-alpha, at 100-ug/kg concentration, was delivered for seven days via mini-osmotic pumps to C57BL/6 mice. Sham treated mice received 0.1 % murine serum albumin in sterile saline via mini-osmotic pumps for seven days. Following seven days of treatment, extensor digitorum longus (EDL) and soleus muscles were dissected out and analyzed for neutrophil and macrophage concentrations via immunohistochemistry. Overt signs of skeletal muscle injury and regeneration were assessed via histological staining. RESULTS In EDL muscles from TNF-alpha treated mice, neutrophil and macrophage concentrations were elevated six and three fold respectively, compared to the sham treated mice. Neutrophil and macrophage concentration were also elevated five and two fold respectively, in soleus muscles from TNF-alpha treated mice compared to sham treated mice. No overt signs of muscle injury were observed in EDL muscles, but modest signs of muscle injury were present in soleus muscles from TNF-alpha treated mice. Furthermore, signs of muscle regeneration were not present in either EDL or soleus muscle from TNF-alpha treated mice. CONCLUSIONS TNF-alpha promotes inflammation in skeletal muscle as indicated by the accumulation of neutrophils and macrophages. Further investigation is needed to determine the role of inflammatory cells in cachexia. Supported by an award from the American Heart Association Ohio Valley Affiliate and an ACSM Foundation Research Grant