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 micrograms protein/micrograms DNA, means +/- SD, both P less than 0.001). Muscle protein synthesis, calculated by comparing the incorporation of 13C-leucine into biopsy samples taken after an 8 h L-[1-13C] 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 greater than 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 less than 0.05). Patients taking corticosteroids had a markedly depressed rate of muscle protein synthesis (0.035 +/- 0.008% h-1, P less than 0.05) and reduced intra-muscular PGF 2 alpha concentration (P less than 0.01). We conclude that steroid therapy significantly influences the mechanism of skeletal muscle atrophy in patients with rheumatoid arthritis.
Gibson
J N
JN
Department of Orthopaedic Surgery, Edinburgh University, Scotland, UK.
Poyser
N L
NL
Morrison
W L
WL
Scrimgeour
C M
CM
Rennie
M J
MJ
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis*; D009132:Muscles / Q000378:metabolism; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism; D011239:Prednisolone / Q000627:therapeutic use
D009124:Muscle Proteins; D011239:Prednisolone; D015237:Dinoprost