ADJUVANT ARTHRITIS AS A MODEL OF INFLAMMATORY CACHEXIA

Objective. To determine whether adjuvant arthritis (AA) leads to chang es in body composition and cytokine production similar to those seen i n 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 K -42 gavage, Splenocyte production of interleukin-1 (IL-1) and tumor ne crosis factor alpha (TNF alpha) was measured by bioassay, Weight and f ood 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 o f 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-four th of the weight lost by the animals with AA (P < 0.01), indicating th at anorexia alone does not explain inflammatory cachexia, Weight loss was correlated with TNF alpha production by spleen mononuclear cells ( r = 0.68, P < 0.007), and a weaker correlation was seen with IL-1 prod uction (r = 0.15, P < 0.04). Conclusion. AA in rats is a useful model of inflammatory cachexia that mimics the human pathophysiology in impo rtant ways, and is consistent with cytokine-driven cachexia in chronic inflammatory arthritis.