BENEFICIAL-EFFECTS OF ENDOTOXIN TREATMENT ON METABOLISM IN TUMOR-BEARING RATS

The effects of endotoxin treatment on host metabolism in tumour-bearing rats were investigated. Metabolism in control rats (non-tumour-bearing) was slightly altered by endotoxin treatment, whereas in tumour-bearing rats a number of biochemical parameters that were intially perturbed by the presence of the tumour had returned to normal at 48 h post-treatment. The beneficial effects included increased blood glucose and insulin concentrations, and decreased ketone body, triglyceride and lactate concentrations. Potentially non-beneficial effects of endotoxin observed in both tumour-bearing and control rats included decreased plasma cholesterol, and increased plasma phosphate, potassium and alkaline phosphatase levels. Endotoxin caused haemorrhaging in the encapsulated tumour, and this was associated with histological evidence of endothelial damage, red cell infiltration into surrounding tumour tissue and a marked decrease in cell viability. The in vivo uptake of glucose by the tumour, measured by 2-deoxy [U-C-14]glucose uptake, was decreased by 96% following endotoxin treatment, and this was associated with a two-fold increase in glucose uptake by muscle. It is concluded that endotoxin treatment has major effects on cell viability and the integrity of vasculature in the tumour, which limits glucose uptake by the tumour and thereby decreases the energy and substrate requirements of the tumour, thus benefiting the host. It is suggested that tumour cytotoxicity and intra-tumour haemorrhage are the result of endotoxin stimulating cytokine release from macrophages that are already activated by the presence of the tumour. While the effects of endotoxin on metabolism in tumour-bearing rats appeared to be primarily the result of anti-tumour activity, other findings, particularly the raised plasma alkaline phosphatase activity that was observed in endotoxin-treated control and tumour-bearing rats, indicate possible side effects that may need to be considered in any treatment strategy.