Protein metabolism in rheumatoid arthritis and aging. Effects of muscle strength training and tumor necrosis factor α

Abstract

Objective. To determine the effects of rheumatoid arthritis (RA) on whole-body protein metabolism.Methods. We examined protein metabolism and its hormonal and cytokine mediators before and 12 weeks after progressive resistance muscle strength training in 8 healthy young (mean k SD age 25 2 2 years) and 8 healthy elderly (70 rt 5 years) men and women, and in 8 adults with RA (42 2 13 years). An additional 6 healthy elderly subjects (69 k 3 years) served as a swimming-only control group.Results. Subjects with RA had higher rates of protein breakdown than did young or elderly healthy subjects (79.9 f 17.2 versus 60.3 f 5.8 and 63.7 2 12.4 pmoles/gm total body potassium/hour, respectively, P < 0.05), while there was no effect of age per se. Patients treated with methotrexate had normal rates of protein breakdown (P < 0.01 versus RA without methotrexate; P not significant versus healthy young subjects). Increased protein catabolism in RA was no longer evident after strength training. In multiple regression analysis, levels of tumor necrosis factor a (TNFa) (r = 0.47, P = 0.01) and growth hormone (r = -0.51, P = 0.006) were associated with protein breakdown, and plasma glucagon levels were inversely correlated with protein synthesis (r = -0.45, P =0.02). Growth hormone (r = -0.56, P = 0.002) and glucagon (r = 0.45, P = 0.04, levels were associated with protein oxidation.Conclusion. Adults with RA have increased whole-body protein breakdown, which correlates with growth hormone, glucagon, and TNFa production.Despite the many advances in our understanding of the disordered immune response that occurs in rheumatoid arthritis (RA), little information has been available about the effect of inflammation on metabolism and body composition in RA. Previous work from our laboratory has shown that body cell mass and physical activity are significantly reduced, and resting energy expenditure (REE) significantly increased, in patients with RA compared with healthy age-, sex-, race-, and weight-matched controls (1-3). This hypermetabolism of RA (defined as an increase in REE by >lo% above predicted levels) was directly associated with the production of tumor necrosis factor a (TNFa) and interleukin-lp (IL-1p) by peripheral blood mononuclear cells (PBMC) from these patients, which was approximately 2-fold higher than that in the control subjects. We have termed the cytokine-associated loss of lean body mass in RA rheumatoid cachexia, and have proposed that this cachexia is an important contributor to morbidity and mortality in RA, and offers insights into inflammatory mediators of cachexia (4).Understanding the mediators of the decline in body cell and protein mass is important because loss of more than -40% of baseline body cell mass is fatal, as shown in starvation, aging, and in acute illness (5). In

Musculoskeletal abnormalities of the tibia in juvenile rheumatoid arthritis

“…In our study population, active joint inflammation at the time of study was inversely related, and muscle mass was positively related, to trabecular vBMD. Increased cytokine production, which occurs during active inflammation, is known to increase muscle catabolism and bone resorption (36,37). Thus, we speculate that increased cytokine production is responsible for trabecular bone loss in children with JRA.…”

Metabolism in Patients with Rheumatoid Arthritis: Resting Energy Expenditure, Physical Activity and Diet-Induced Thermogenesis. Invited Review

“…In particular, protein intake, the main nutrient that contributes to increased fat-free mass, is not significantly different between RA with young and older healthy controls [73]. As such, based on the current evidence, the occurrence of rheumatoid cachexia does not seem to be diet-dependant.…”

Asymptomatic Pericardial Effusion in Patients with Rheumatoid Arthritis

“…Hypoalbuminemia is frequently encountered in RA, and earlier studies indicate that increased loss of serum albumin consumed at the site of inflammation, cytokine mediated intravascular catabolism and/or inadequate food intake contributes to hypoalbuminemia in patients with RA [9,10,11,12,13]. Moreover, protein hypermetabolism of chronic inflammation is reported to persist even when good clinical control of RA is achieved [11, 12]. Although there were no significant differences in the duration of RA and RF titer between the patients with and without hypoalbuminemia, we found that patients with hypoalbuminemia had a significantly higher C-reactive protein level and hypoalbuminemia was more remarkable in patients with high C-reactive protein.…”

“…Acute-phase proteins are defined as one whose plasma concentration increases (positive acute-phase proteins) or decreases (negative acute-phase proteins) during inflammatory disorder [8]. Serum albumin has been reported to fall in severe inflammatory states and hypoalbuminemia is frequently encountered in RA [9,10,11,12,13]. Because no one has assessed the two major pathophysiologic bases causing PE in patients with RA, we designed a study to determine the frequency and clinical correlates associated with the occurrence of asymptomatic PE in patients with RA.…”