TNF-alpha and cortisone impair peptide chain initiation by altering the availability of initiation factor EIF-4E

The effect of chronic tumor necrosis factor-a (TNF-a) and cortisone treatment on the concentration of translational initiation factor eIF-4E in rat skeletal muscle was evaluated. Crude muscle extracts from control and experimental groups (TNF-a s.c. @ 50 microg/kg body wt each day for 5 days or cortisone s.c. @ 100 mg/kg body wt for 5 days) were used to purify eIF-4E by immunoprecipitation and polyacrylamide gel electrophoresis (PAGE) followed by Western blot analysis. Quantification of eIF-4E was done by densitometry. Both TNF-a and cortisone induced a marked decline in the concentration of eIF-4E in rat skeletal muscle. There was no difference in the ratio of phosphorylated to unphosphorylated eIF-4E after TNF-a treatment. These findings suggest that both TNF-a and cortisone inhibit peptide chain initiation in skeletal muscle cells by decreasing the expression of eIF-4E.