Use of recombinant human soluble TNF receptor in anorectic tumor-bearing rats

Abstract

With progression of tumor growth, rats demonstrate anorexia and reduced food intake, a function of meal number and meal size. Tumor necrosis factor-alpha (TNF-alpha), a recognized anorectic agent, reacts with two different receptors (type I: 55 kDa; type II: 75 kDa). We used a dimeric, pegylated 55-kDa TNF receptor construct to test its effects on food intake, meal number, and meal size, which were continuously measured with a rat eater meter in 16 Fischer 344 male rats injected with 10(6) viable methylcholanthrene cells. When anorexia developed, rats received a subcutaneous injection of either 0.25 mg/kg body wt of soluble TNF receptor construct (study) or vehicle (tumor-bearing control). Before TNF inhibitor injection, no differences were observed in food intake, meal number, or meal size between the two groups. After the TNF inhibitor injection, study vs. control rats significantly improved food intake as a result of an increase in meal number and meal size. Rats also showed a significant improvement in body weight. These data suggest that TNF-alpha, in addition to other cytokines, contributes to the anorexia of tumor growth, probably mediated via the hypothalamus.