Cachectin activity in the serum of cachectic, tumor-bearing rats
M. C. Stovroff, D. L. Fraker and J. A. Norton
Surgical Metabolism Section, National Cancer Institute, Bethesda, MD 20892.
Cachectin/tumor necrosis factor has been postulated to be a possible
mediator of cancer cachexia. Using a sensitive bioassay, we attempted to
detect circulating cachectin activity in the serum of sarcoma-bearing rats
and to correlate levels with measurements of cachexia and the extent of
disease. In addition, we resected the tumor to determine the time course of
reversal of cachexia and the disappearance of cachectin activity in the
serum. Circulating cachectin activity was not detectable in the serum of
non-tumor-bearing rats or in tumor-bearing rats until 28 days after
implantation. With evidence of food intake and body weight decline,
cachectin activity became detectable in the serum and levels increased as
cachexia and tumor burden increased. Serum cachectin activity levels
correlated directly with tumor burden and inversely with food intake and
body weight change. After resection of the tumor, food intake and body
weight increased and serum cachectin activity became undetectable. Serum
triglyceride levels were higher in cachectic tumor-bearing rats than in
pair-fed non-tumor-bearing controls, and levels decreased after tumor
resection as cachectin activity decreased. The results suggest that
cachectin is a humoral mediator of cachexia in this rat-tumor model.
