Cachectic effects of recombinant human tumor necrosis factor in rats.

Treatment of rats with either intermittent bolus i.v. injections or continuous i.

Tumor necrosis factor: immune endocrine interaction.

Tumor necrosis factor (TNF), a peptide produced by macrophages in response to endotoxin, has been implicated as a mediator of septic shock. This study examined the effects of injections of recombinant (r) human TNF on circulating levels of metabolic substrates and hormones in conscious, unrestrained rats and the effects of TNF on cortisol secretion from human adrenocortical cells in vitro. Sublethal doses of rTNF--doses that did not produce hemodynamic changes in previous work--produced rapid (1 hour), significant increases in blood levels of glucose, lactate, and triglycerides and decreases in plasma levels of branched chain amino acids.

Body composition changes in rats with experimental cancer cachexia: improvement with exogenous insulin.

Exogenous insulin treatment has been shown to improve food intake and host weight of cachectic tumor-bearing (TB) rats, but the composition of the host weight gain has not been quantitated. Sixty-six Fischer 344 rats were randomized to seven groups: early nontumor-bearing (NTB) (n = 10) who underwent compositional analysis (CA) on the day the methylcholanthrene sarcoma was implanted in TB rats; pretreatment-NTB (n = 10) and pretreatment-TB (n = 10) who underwent CA 25 days later when rats began treatment with saline or insulin; and finally saline-treated NTB (n = 9), saline-treated TB (n = 9), insulin-treated NTB (n = 9), and insulin-treated TB (n = 9), who underwent CA following 5 days of treatment with daily saline or neutral protamine hagedorn insulin 2 units/100 g. Body weight and food intake were measured daily.

Gluconeogenesis in the tumor-influenced rat hepatocyte: importance of tumor burden, lactate, insulin, and glucagon.

In an attempt to define the relationship between tumor burden (cachexia) and host hepatocyte gluconeogenesis, the following experiments were performed with the use of an F344 male rat bearing a transplantable sarcoma. Food intake of tumor-bearing (TB) rats was constant until day 24 following implant and a tumor burden of 18 +/- 5.2% (mean +/- SD), at which time food intake progressively declined daily.

Altered leucine metabolism in noncachectic sarcoma patients.

Leucine and whole body protein metabolism were quantitated in 26 human subjects (6 sarcoma patients, 20 age-matched normal controls) using a primed, continuous infusion of [13C]leucine. Plasma samples were analyzed every 15 min for enrichment of [13C]leucine. Plateau enrichment levels were then used to calculate whole-body protein turnover, synthesis, and breakdown rates.