Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation.

Abstract

The cytokines IL-10 and TNF-a cause cachexia and hypermetabolism in animal models, but their role in human inflammation remains controversial. The relationship between in vitro cytokine production and metabolism was examined in 23 adults with RA and 23 healthy control subjects matched on age, sex, race, and weight. Body composition was measured by multicompartmental analysis of body cell mass, water, fat, and bone mass. Resting energy expenditure (REE) was measured by indirect calorimetry. Cytokine production by PBMC was measured by radioimmunoassay. Usual en4gy intake, physical activity, disability scores, medication use, and other confounders were also measured.Body cell mass was 13% lower (P < 0.00001), REE was 12% higher (P < 0.008), and physical activity was much lower (P < 0.001) in subjects with RA. Production of TNF-a was higher in RA than controls, both before and after stimulation with endotoxin (P < 0.05), while production of IL-1,# was higher with endotoxin stimulation (P < 0.01). In multivariate analysis, cytokine production was directly associated with REE (P < 0.001) in patients but not in controls. While energy and protein intake were similar in the two groups and exceeded the Recommended Dietary Allowances, energy intake in subjects with RA was inversely associated with IL-1,B production (P < 0.005).In this study we conclude that: loss of body cell mass is common in RA; cytokine production in RA is associated with altered energy metabolism and intake, despite a theoretically adequate diet; and TNF-a and IL-1,8 modulate energy metabolism and body composition in RA. (J. Clin. Invest. 1994. 93:2379-2386 Key words: body composition * interleukin-1l tumor necrosis factor * energy * metabolism

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

“…Leucine flux at baseline-a measure of whole-body protein turnover, and in the fasting state, equals protein breakdown-was directly associated with TNFa production (Figure 3). TNFa production was increased in patients with RA compared with controls in this study and in our previous studies (2,3). These findings suggest that elevated TNFa levels lead to increased protein breakdown in patients with 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)(2)(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.…”

Validity of reported energy expenditure and reported intake of energy, protein, sodium and potassium in rheumatoid arthritis patients in a dietary intervention study

“…Furthermore, when estimating the TEE by means of the AR, the PAL-value obtained was multiplied by the BMR estimated using the equations by the Department of Health (1991), which are standard equations not specifically developed for individuals with RA. In a study by Roubenoff et al (1994), the resting energy expenditure (REE), after adjustment for body cell mass, was found to be higher in RA patients compared to healthy controls. Furthermore, in the group of RA patients the REE increased with the cytokine production.…”

Sarcopenia and its implications for the elderly

“…Such a situation has been clearly demonstrated for acute illness and for chronic in¯ammatory conditions such as rheumatoid arthritis and HIV infection (Roubenoff et al, 1994). There is moderately strong evidence that aging is associated with immune senescence that includes loosening of the tolerance which allows a healthy immune system to correctly identify`self ' from`non-self ' antigens and avoid targeting self antigens.…”