ACUTE TREATMENT WITH TUMOR-NECROSIS-FACTOR-ALPHA INDUCES CHANGES IN PROTEIN-METABOLISM IN RAT SKELETAL-MUSCLE

Acute treatment of rats with recombinant tumour necrosis factor (TNF-alpha) caused an enhanced proteolytic rate - measured as tyrosine released in the presence of cycloheximide - in soleus muscle (34%). The cytokine treatment also decreased the rate of protein synthesis in this muscle (22%) while it had no effect upon the same parameter in extensor digitorum longus (EDL) (26%) muscle. In addition, treatment of rats with TNF-alpha increased amino acid uptake by transport system A in the incubated muscles both in soleus (45%) and EDL (99%) in the presence of insulin in the incubating medium. This effect was not associated with a direct action of TNF on muscle since the addition of different concentrations of the cytokine to the preparations did not alter the uptake of alpha-(methyl)-aminoisobutyric acid by the incubated muscles. It can be concluded that acute TNF-alpha. treatment causes changes in protein metabolism in red-type muscles - such soleus - while little effects are seen in white-type muscles - such as EDL. The results presented may, to some extent, be related to the cachectic response associated with cancer and inflammation.