Reduced Toxicity of Irradiated Endotoxin in Mice Compromised by Irradiation, Tumors, or Infections

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Abstract
Endotoxin (LPS [lipopolysaccharide]) exposed to 100-200 KiloGrays of .gamma. radiation did not induce rabbit platelet aggregation in vitro and had reduced ability to cause mitogenesis of B lymphocytes from C57BL/6 mice. When tested in B6CBF1 mice exposed to 10 Grays 60Co radiation 3 or 7 days previously, 300 .mu.g of irradiated LPS caused no deaths; 300 .mu.g of unirradiated LPS, which caused no mortality in unirradiated mice, killed 60 and 44% of the mice when given on days 3 or 7 post-radiation, respectively. Of C57BL/6 mice engrafted with 5 .times. 106 Lewis lung carcinoma cells 3 days before challenge with 300 .mu.g of normal LPS, 60% died. No animals given irradiated LPS died. When 100 .mu.g of either LPS preparation was given simultaneously with 105 live Klebsiella pneumoniae, 80-100% mortality was observed. No deaths were observed if 50 .mu.g of irradiated LPS were administered with 105 bacteria; 50 .mu.g of unirradiated LPS caused 100% mortality. Similar mortalities were obtained when 100 .mu.g of either toxin preparation was given 24 h postinfection; these were lower than those obtained with the simultaneous challenge. Endotoxin given 24 h before 105 organisms was less toxic than that given at the other times; irradiated LPS caused fewer deaths than did unirradiated LPS. Similar results were seen when 106 cells were used to challenge mice. Treatment 24 h before challenge caused 70% mortality with unirradiated LPS compared to 30% mortality with irradiated LPS. All mice challenged with 107 bacteria 24 h after treatment with saline or unirradiated LPS died by 72 h postinfection; only 50% mortality was obtained in mice given irradiated LPS. None of these mice died until after 72 h. Thus, under some circumstances, irradiated LPS can be more safely administered [as an immunoenhancer] to animals with compromised resistance than can unirradiated LPS.