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

Ronenn Roubenoff, Rebecca A. Roubenoff, Joseph G. Cannon, Joseph J. Kehayias, Hong Zhuang, Bess Dawson-Hughes, Charles A. Dinarello, Irwin H. Rosenberg

Research output: Contribution to journalArticlepeer-review

511 Scopus citations


The cytokines IL-1β and TNF-α 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 energy 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-α was higher in RA than controls, both before and after stimulation with endotoxin (P < 0.05), while production of IL-1β 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-1β 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-α and IL-1β modulate energy metabolism and body composition in RA.

Original languageEnglish (US)
Pages (from-to)2379-2386
Number of pages8
JournalJournal of Clinical Investigation
Issue number6
StatePublished - Jun 1994
Externally publishedYes


  • body composition
  • energy
  • interleukin-1
  • metabolism
  • tumor necrosis factor

ASJC Scopus subject areas

  • Medicine(all)


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