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

Giovanni F. Torelli, Michael M. Meguid, Lyle L. Moldawer, Carl K. Edwards, Hyune Ju Kim, Janna L. Carter, Alessandro Laviano, Filippo Rossi Fanelli

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

With progression of tumor growth, rats demonstrate anorexia and reduced food intake, a function of meal number and meal size. Tumor necrosis factor- α (TNF-α), 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 106 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-α, in addition to other cytokines, contributes to the anorexia of tumor growth, probably mediated via the hypothalamus.

Original languageEnglish (US)
Pages (from-to)R850-R855
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume277
Issue number3 46-3
DOIs
StatePublished - Sep 1999

Keywords

  • Cancer anorexia
  • Feeding behavior
  • Food intake regulation
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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