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 ~10⁵ to ~10⁹ colony-forming units (CFU). Significant dose-related increases in plasma adrenocorticotropin and corticosterone occurred after ~10⁷ CFU. Fever occurred after ~10⁷ CFU but not after ~10⁹ 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 ≤240 min to 5.1 ± 0.9 endotoxin units (EU)/ml after ~10⁷ CFU and to 440 ± 59 EU/ml after ~10⁹ CFU. Endotoxin at ~10⁹ 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 ~10⁷ 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.