Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #165846
Title: PATIENTS WITH RHEUMATOID ARTHRITIS [RA] HAVE LOW PROTEIN SYNTHESIS RATES AND ELEVATED TUMOR NECROSIS FACTOR-A (TNF-ALPHA) AND TRANSFORMING GROWTH FACTOR-B (TGF-BETA) TRANSCRIPT LEVELS IN SKELETAL MUSCLE

Author
item WALSMITH, JOSEPH - ASTRAZENECA PHARM
item VANNIER, EDOUARD - TUFTS-HNRCA
item YARASHESKI, KEVIN - WASHINGTON UNIVERSITY
item WITSELL, ALICE - UMASS MEDICAL CENTER
item PARKER, RUSSELL - TUFTS-HNRCA
item LEMMER, JEFFREY - MICHIGAN STATE UNIVERSITY
item ROUBENOFF, RONENN - MILLENNIUM PHARM

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/1/2003
Publication Date: 10/25/2003
Citation: Walsmith, J., Vannier, E., Yarasheski, K., Witsell, A., Parker, R., Lemmer, J., Roubenoff, R. 2003. Patients with rheumatoid arthritis[RA] have low protein synthesis rates and elevated Tumor Necrosis Factor-alpha(TNF-alpha) and Transforming Growth Factor-beta (TGF-beta) transcript levels in skeletal muscle [abstract]. Arthristis and Rheumatism. 48(9 Suppl):S104.

Interpretive Summary:

Technical Abstract: We have previously shown that rheumatoid arthritis is associated with a loss of skeletal muscle mass, elevated resting metabolic rate, and accelerated whole body protein degradation, which are associated with excess systemic production of the catabolic cytokines interleukin-1-beta (IL-1-beta) and TNF-alpha. To date, the effect of rheumatoid arthritis on skeletal muscle inflammation and protein metabolism has not been well investigated. We examined skeletal muscle protein synthesis (SMPS) and gene expression of several catabolic/anti-anabolic cytokines (TNF-alpha, IL-1-beta, and TGF-beta) in skeletal muscle from 8 patients with moderate, medically treated rheumatoid arthritis and 8 age-, sex-, and BMI-matched healthy controls [C]. SMPS are was determined in vivo by measuring the rate of incorporation of leucine into skeletal muscle protein during a 6-hour IV infusion of [13C]leucine. mRNA levels of TNF-alpha, IL-1-beta and TGF-beta were measured by quantitative RT-PCR of muscle biopsy samples. The SMPS rate was 25% lower in rheumatoid arthritis compared with C, and mean TNF-alpha and TGF-beta mRNA levels were 3.0-fold (p<0.02) and 4.0-fold (p<0.007) higher in rheumatoid arthritis compared with C. Mean IL-1-beta mRNA levels did not differ between rheumatoid arthritis and C (p=0.59). TNF-alpha and TGF-beta mRNA levels were inversely correlated with SMPS rate (r=-0.52, p=0.05; r=-0.50, p=0.07) and mRNA levels of TNF-alpha and TGF-beta were positively correlated with each other in rheumatoid arthritis (r=0.78, p=0.02). These data are the first to show reduced SMPS in rheumatoid arthritis. The magnitude of this difference was large, and is comparable to the ~20% lower SMPS rate observed by Yarasheski et al. in patients with AIDS-wasting compared with HIV+ asymptomatic patients. These data also associate TNF-alpha and TGF-beta with reduced SMPS and indicate that TNF-alpha and TGF-beta gene expression is linked in rheumatoid arthritis. We conclude: 1) that reduced SMPS may be an important contributor to loss of skeletal muscle mass in rheumatoid arthritis; and 2) that the well-established protein depleting effects of TNF-alpha on skeletal muscle may, in part, be mediated and/or potentiated by TGF-beta.