Tumor Necrosis Factor, Interleukin 1, and Interleukin 6 in Experimental Cancer Cachexia

Abstract

Anorectic, weight-losing Fischer 344 rats bearing a methycholantherene-induced (MCA) sarcoma received intraperitoneal injections of rabbit antiserum raised against murine tumor necrosis factor-a at 14, 18, and 25 days after tumor induction. Treatment of tumor-bearing rats with TNF antiserum delayed the onset and significantly reduced the decline in mean 12-hour daytime and nighttime intra-abdominal temperatures on days 18 through 25. However, anti-TNF antibody treatment did not alter the declines in carcass weight or motor activity measured from day of tumor induction until death, or reduce the tumor burden at death. In a separate experiment, an intraperitoneal injection of interleukin 1 receptor antagonist protein (IL-1ra) to cachectic, tumor-bearing rats had during the first 24 hours following treatment or for the next 5 days until the experiment ended. We conclude that an endogenous TNF response may be one of the factors involved in the development of cancer anorexia, and that this cytokine has temperature-lowering properties.