Studies on Distribution of Escherichia coli Endotoxin in Mice.

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Abstract
Endotoxin was prepared by trichloroacetic acid extraction followed by ethanol f ractionation. It was tagged by incubation with the isotope Cr51Cl3. Excess Cr51Cl3 was removed by lengthy dialysis. Assay for in vivo endotoxin was accomplished by digestion of specimens in acid and measurement of radioactivity in a well-type scintillation counter. The LD50 dose of endotoxin for 18 to 20 g mice was 145 [mu]g intravenously and intracranially, 290 [mu]g intraperitoneally and 580 [mu]g intramuscularly. In mice receiving intravenous sublethal doses of endotoxin approximately 60% of injected radioactivity was still present in the liver 60 days later. Intravenous injection of larger doses resulted in a marked increase in circulating endotoxin as dosages reached the lethal range. This did not represent organ saturation with subsequent overflow of endotoxin because the amounts in organs, especially the liver, continued to increase with increases in dosage. Distribution pattern of endotoxin in mice injected intracranially was similar to that of mice injected intravenously. Distribution pattern of mice injected intramuscularly differed markedly from those found in mice injected intravenously or intracranially in that much of the endotoxin remained at the site of injection, very little radioactivity was found in organs, and blood levels of endotoxin increased rather than decreased during the first 24 hours, Premedication of mice with trypan blue resulted in greater susceptibility to endotoxin and increased amounts of circulating endotoxin in mice injected intramuscularly or intravenously. Using the technique described, lethality of endotoxin for mice could not be related to any one distribution pattern.

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