Role of endotoxin in the response to experimentally induced bacteremia in chronically prepared rats

Chronically prepared rats were injected intravenously with live Escherichia coli in doses from similar to 10(5) to similar to 10(9) colony-forming units (CFU). Significant doserelated increases in plasma adrenocorticotropin and corticosterone occurred after similar to 10(7) CFU. Fever occurred after -10i CFU but not after similar to 10(9) CFU. These responses changed significantly but were not blocked completely when >94% of the viable E. coli was removed from the inoculates. The remaining endotoxin activity in the inoculates resembled lipopolysaccharide (LPS) extracted from the same strain of E. coli on electrophoretic gels. Plasma endotoxin increased for greater than or equal to 240 min to 5.1+/-0.9 endotoxin units (EU)/ml after similar to 10(7) CFU and to 440+/-59 EU/ml after similar to 10(9) CFU. Endotoxin at similar to 10(9) CFU caused death within 24 h that was not predicted by the total activity of endotoxin that was injected. In contrast, extracted LPS with its strain and total activity matched to similar to 10(7) CFU mimicked the responses to this nonfatal dose. The total endotoxin activity of the injected bacteria appears to account for the effects of nonfatal doses of E. coli but not for the effects of fatal doses.