THE ESSENTIAL ROLE OF THE LIVER IN DETOXIFICATION OF ENDOTOXIN
WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
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Cell-free homogenates of several tissues of the guinea pig were capable of inactivating endotoxin in vitro. High degrees of activity were found in the kidney, which is not thought to possess much reticuloendothelial tissue, as well as in the spleen and liver, which are rich in phagocytic cells. Animals which had undergone splenectomy were no more susceptible to the lethal effect of endotoxin than sham-operated controls, indicating that the spleen probably plays no more than a minor role in the response of the guinea pig to endotoxin. Damage to the hepatic parenchyma with carbon tetrachloride increased susceptibility of the animals approximately 200-fold. Maximal susceptibility was correlated with the presence of a maximal amount of necrosis in the liver, and liver tissue removed at this stage of intoxication showed almost no ability to detoxify endotoxin in vitro. Healing of the lesion in the liver was associated with a return toward normal resistance to endotoxin by the animal and with a reappearance of endotoxin-inactivating capacity of liver tissue homogenates. Inactivation of endotoxin by guinea pig liver homogenates and mitochondria appeared to be due to activation and oxidation of the fatty acid portion of the endotoxin molecule, a finding which implies that the lipid component of endotoxin is necessary for its toxicity.