Susceptibility of Rabbits to Pyrogenic and Lethal Effects of Endotoxin after Acute Liver Injury ∗

Summary

Administration of a single large sublethal dose of CCl₄ in the rabbit results in severe centrilobular hepatic necrosis and acute derangement of liver function, followed by rapid healing. At the height of the lesion (48 hours) animals are approximately 120 times more susceptible than normal animals to the lethal effect of bacterial endotoxin, whereas animals tested 7 days after CCl₄ are only 4 times as susceptible as normals. Measurement of the 5-hour fever index following small doses of endotoxin (10^-4 to 10^-5 LD₅₀) reveals that animals tested 48 hours after CCl₄ are approximately 40 times more susceptible than normal rabbits to the pyrogenic action of endotoxin. Animals tested 5 days after CCl₄ show only a normal febrile response. Normal rabbit liver is capable of detoxifying endotoxin in vitro, whereas liver from CCl₄-treated rabbits is not. Results of these studies indicate that acute CCl₄-induced liver injury in the rabbit is associated with enhanced susceptibility to both lethal and pyrogenic effects of bacterial endotoxin.