Distribution of chromate-labeled Brucella abortus endoxin in tolerant mice.

Endotoxin tolerance as manifested by a lesser degree of hypoferremia was demonstrated in mice when both pretreatment (10 mug per injection) and challenge (100 mug) does of Brucella abortus endotoxin were administered intraperitoneally. Qualitative and quantitative studies on the distribution of chromate-labeled endotoxin in normal mice revealed that the endotoxin localized predominately in the liver and hypoferremia could be related to a high uptake of endotoxin by this organ. In tolerant mice, the labeled endotoxin was found mainly in the mesenteric lymph nodes (MLN) with smaller quantities in the blood, spleen, and liver. Experiments with splenectomized mice provided supporting evidence that the liver was the target organ of the hypoferremic response to endotoxin. High localization of endotoxin in the MLN with lower quantities in the blood, livers, and spleens of tolerant mice indicated that tolerance may be the result of a blockage by the MLN, preventing the endotoxin from reaching the liver. This inference was supported by the finding that hypoferremic tolerance did not occur when the hypoferremia-provoking dosage of endotoxin (100 mug) was given intravenously to mice pretreated intraperitoneally. There was less hypoferremia in normal mice injected with a mixture of antiserum and 100 mug of endotoxin than in mice given the same dosage of endotoxin in saline. Distribution studies on endotoxin treated with specific antiserum revealed that the endotoxin localized principally in the MLN, thus preventing most of the endotoxin from reaching the liver, the target organ of the hypoferremic response.