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.
Department of Orthopaedic Surgery, Edinburgh University, Scotland, UK.
J N
JN
Gibson
N L
NL
Poyser
W L
WL
Morrison
C M
CM
Scrimgeour
M J
MJ
Rennie
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