Growing tumors induce hypersensitivity to endotoxin and tumor necrosis factor.
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.
D000818:Animals; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D006023:Glycoproteins / Q000633:toxicity*; D007928:Lethal Dose 50; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D009374:Neoplasms, Experimental / Q000503:physiopathology*; D012513:Sarcoma, Experimental / Q000503:physiopathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha
D004731:Endotoxins; D006023:Glycoproteins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha