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Use of recombinant human soluble TNF receptor in anorectic tumor-bearing rats
G F Torelli1, M M Meguid, L L Moldawer
1Surgical Metabolism and Nutrition Laboratory, Department of Surgery, University Hospital, State University of New York Health Science Center, New York, NY 13210, USA.
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.
Insights
Tumor necrosis factor-alpha (TNF-alpha) contributes to cancer-induced anorexia. Blocking TNF-alpha with a soluble receptor construct improved food intake and body weight in tumor-bearing rats.
Area of Science:
- Oncology
- Neuroscience
- Physiology
Background:
- Tumor growth often leads to anorexia and reduced food intake in rats.
- Tumor necrosis factor-alpha (TNF-alpha) is a known factor that causes anorexia.
- TNF-alpha interacts with type I (55 kDa) and type II (75 kDa) receptors.
Purpose of the Study:
- To investigate the effect of a soluble TNF receptor construct on food intake in tumor-bearing rats.
- To determine if TNF-alpha mediates anorexia associated with tumor growth.
Main Methods:
- 16 Fischer 344 male rats were injected with methylcholanthrene cells to induce tumors.
- Food intake, meal number, and meal size were continuously monitored using a rat eater meter.
- Rats received either a soluble TNF receptor construct or a vehicle control after anorexia developed.
Main Results:
- Rats treated with the TNF receptor construct showed significant improvements in food intake.
- The enhanced food intake was due to an increase in both meal number and meal size.
- Body weight also significantly improved in the treated group compared to controls.
Conclusions:
- TNF-alpha plays a significant role in mediating tumor-induced anorexia.
- Inhibition of TNF-alpha can ameliorate anorexia and improve body weight during tumor progression.
- The hypothalamus is a likely site for TNF-alpha's anorectic effects.