Increased Lethality After Endotoxin in Old or Leukemic AKR Mice 1 2

Summary Lethality following a single injection of Salmonella typhosa endotoxin (LPS) was found to be higher for 6- to 10-month “old” AKR than for “young” adult (3 months 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 both 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. Reticuloendothelial function as measured by rate of clearance of colloidal carbon 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. The present studies showed no differences between young and old in degree of small intestine weight loss or rate of recovery after 700 rads X-ray exposure. 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. These data suggest that 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.