Increased Lethality After Endotoxin in Old or Leukemic AKR Mice

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Abstract
Lethality following a single injection of Salmonella typhosa endotoxin (LPS) was higher for 6 to 10 mo. old AKR than for young adult (3 mo. old) of the same strain. Young AKR mice with transplanted lymphoma were also more sensitive to the lethal effects of endotoxin than the nonlymphomatous young mice. Exposure to radiation 3 days prior to endotoxin injection increased sensitivity in the normal young mice and the old AKR mice but significant increases were seen at lower radiation doses in the old mice. Old mice were more sensitive to the radiation than young mice. Several possible causes for differences observed were investigated. RES function as measured by rate of clearance of colloidal C from blood was the same for young and old mice. Previous studies have implicated the gut in the increased sensitivity to endotoxin seen 3 days after radiation. No differences between young and old in degree of small intestine weight loss or rate of recovery after 700 rads X-ray exposure were found. Although counts of blood granulocytes were somewhat higher and platelets were somewhat lower for the young tumor-bearing and old mice as compared to young controls, it is not obvious how this might affect the differences in LPS sensitivity observed. Effects of old age, lymphoma or combined old age and radiation may lead to unexpected lethal effects from relatively small doses of endotoxin. The biological reason for this increased sensitivity remains obscure.

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