Tumor necrosis factor-alpha and muscle wasting: a cellular perspective

Tumor necrosis factor-alpha (TNF-alpha) is a polypeptide cytokine that has been associated with muscle wasting and weakness in inflammatory disease. Despite its potential importance in muscle pathology, the direct effects of TNF-alpha on skeletal muscle have remained undefined until recently. Studies of cultured muscle cells indicate that TNF-alpha disrupts the differentiation process and can promote catabolism in mature cells. The latter response appears to be mediated by reactive oxygen species and nuclear factor-kappaB which upregulate ubiquitin/proteasome activity. This commentary outlines our current understanding of TNF-alpha effects on skeletal muscle and the mechanism of TNF-alpha action.