Growing tumors induce hypersensitivity to endotoxin and tumor necrosis factor

Abstract

Lewis lung carcinoma and EMT6 sarcoma growing as solid tumors in mice caused a gradual increase in the susceptibility of the animals to lethal toxicity of endotoxins (lipopolysaccharides [LPS]). By day 15 following inoculation of the tumors, the 50% lethal dose of LPS, which in normal mice was approximately 400 micrograms, decreased to 2 micrograms for the sarcoma-bearing mice and 0.1 microgram for the carcinoma-bearing mice. This sensitization to endotoxin was paralleled by a high sensitization to tumor necrosis factor (TNF). Human recombinant TNF given to normal mice was lethal at about 500 micrograms. It was lethal for 50% of the animals bearing EMT6 or Lewis lung carcinoma tumors in amounts of 4 and 0.01 micrograms, respectively, on day 15 following tumor inoculation. The sensitization of tumor-bearing animals to LPS and TNF was paralleled by marked granulocytosis.