MUSCLE PROTEIN-SYNTHESIS IN PATIENTS WITH RHEUMATOID-ARTHRITIS - EFFECT OF CHRONIC CORTICOSTEROID-THERAPY ON PROSTAGLANDIN-F2-ALPHA AVAILABILITY

Using stable-isotope techniques, we measured rates of quadriceps muscle protein synthesis in twelve women with sero-positive rheumatoid arthritis. The results were compared to those from the normal limb of seven women with unilateral osteoarthritis of the knee. Six patients had never received corticosteroid immuno-suppression, but the other six had taken an average of 8 mg Prednisolone per day for 9 years. Quadriceps atrophy was present in both sets of patients with rheumatoid arthritis (normal legs 444 +/- 182, rheumatoid 190 +/- 40, rheumatoid + steroid 300 +/- 110-mu-g protein/mu-g DNA, means +/- SD, both P < 0.001). Muscle protein synthesis, calculated by comparing the incorporation of C-13-leucine into biopsy samples taken after an 8 h L-[1-C-13] leucine infusion with the time averaged enrichment of blood alpha-ketoisocaproate, was 0.056 +/- 0.005% h-1 in the patients not receiving steroids compared with 0.050 +/- 0.02% h-1 in normals (P > 0.05) indicating that muscular atrophy was primarily due to an increase in rate of muscle protein breakdown. Intra-muscular PGE2 concentration was increased in these patients (rheumatoid 0.12 +/- 0.06 ng mg-1 tissue, normals 0.06 +/- 0.03 ng mg-1 tissue, P < 0.05). Patients taking corticosteroids had a markedly depressed rate of muscle protein synthesis (0.035 +/- 0.008% h-1, P < 0.05) and reduced intra-muscular PGF2-alpha concentration (P < 0.01). We conclude that steroid therapy significantly influences the mechanism of skeletal muscle atrophy in patients with rheumatoid arthritis.