Host Resistance to Bacteria in Hemorrhagic Shock. VI. Effect of Endotoxin on Antibacterial Defense.

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Abstract
The mortality rate from one intravenous MLD/100 of Escherichia coli endotoxin was reduced from 100% to 40-60% by ar tibiotic therapy given prior to or at the time of injecting the endotoxin. This was true even if the antibiotic was given orally anc. was completely non-absorbable. Endotoxins from intraintestinal bacteria are thus involved in death from an intravenous MLD/100 of endotoxin. Antibiotics act solely as antibacterial agents, and not as anti-endotoxic agents. A sublethal intravenous dose of endotoxin promptly induced in rabbits an increased sensitivity to a supplementary fractional dose of endotoxin so that a second dose given one hour later increased the mortality from zero to 67%, even though the total of both doses if given as a single initial dose, was not lethal. Recovery of nearly normal resistance to the second dose of endotoxin required about 4 hours. Antibiotics given with the initial dose rendered the second dose harmless; but the same antibiotics given with the second dose did not prevent death. It is inferred that death from the second dose involved the production of additional endotoxin. Reasons are given for inferring that similar phenomena operate in hemorrhagic shock and account for the development of irreversibility to transfusion.