Responses to endotoxin of mice bearing the Lewis lung (3LL) carcinoma

We examined factors which could be responsible for altered sensitivity to endotoxin in tumor bearing mice in order to gain a greater insight into the mechanisms responsible for the toxic effects of the substance. C57BL/6 mice engrafted with 2 × 10⁵ Lewis lung carcinoma cells were injected with 300 μg Salmonella typhosa endotoxin 3,7 and 14 days after tumor cell implantation. A biphasic pattern of mortality was noted when 23 of 35, 1 of 20, and 33 of 34 mice died within 48 hr of injection with endotoxin on days 3, 7 and 14, respectively. Only 1 of 30 normal mice died after injection with this dose of endotoxin. Intestinal penetration by microbial substances did not explain the biphasic sensitivity to endotoxin. Sensitivity to endotoxin seen at day 14 could be associated with tumour mass, but this association would not explain sensitivity to endotoxin at day 3. Regression of tumour growth and decreased tumor-induced mortality was observed in mice injected with 300 μg of endotoxin 7 days after tumor implantation. Larger doses of endotoxin (400–700 μg) had a better therapeutic value but at the expense of increased endotoxin-induced mortality.