Adjuvant arthritis as a model of inflammatory cachexia

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Abstract

Objective. To determine whether adjuvant arthritis (AA) leads to changes in body composition and cytokine production similar to those seen in patients with rheumatoid arthritis.

Methods. AA was induced in Lewis rats using Freund's complete adjuvant. Body cell mass was measured by determining the concentration of total exchangeable potassium using 42K gavage. Splenocyte production of interleukin-1 (IL-1) and tumor necrosis factor α (TNFα) was measured by bioassay. Weight and food intake were also measured.

Results. Animals that developed AA lost 6% of their body weight by the onset of clinically evident arthritis (day 14; P < 0.01) and lost 20% by the end of the inflammatory phase of AA (day 28; P < 0.0001). Body cell mass fell 24.7 ± 8.6% (mean ± SEM) in animals with AA, but did not change significantly in controls (increase of 6.3 ± 7.9%) (P < 0.03). Pair-fed animals lost one-fourth of the weight lost by the animals with AA (P < 0.01), indicating that anorexia alone does not explain inflammatory cachexia. Weight loss was correlated with TNFα production by spleen mononuclear cells (r = 0.68, P < 0.007), and a weaker correlation was seen with IL-1 production (r = 0.45, P < 0.04).

Conclusion. AA in rats is a useful model of inflammatory cachexia that mimics the human pathophysiology in important ways, and is consistent with cytokine-driven cachexia in chronic inflammatory arthritis.

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