Studies on the O Antigen of Salmonella typhosa IV. Endotoxic Properties of the Purified Antigen

A study was made of the endotoxic properties of a protein-free lipopolysac-charide isolated from the 0-901 strain of S. typhosa. The product was lethal for rabbits in a dose range of 20-50 μg while 300-500 μg were required to kill mice. The minimum pyrogenic dose in rabbits was 0.0002 μg, characterizing it as a pyrogen of extremely high potency. In a quantitative study of the local Shwartzman reaction, 1 μg or less, was effective as a preparatory or provocative dose. Its activity in eliciting bilateral renal cortical necrosis, the lesion characteristic of the generalized Shwartzman reaction, was in the range of 5-20 μg. Thus, very small quantities of a lipopolysaccharide, freed of protein, are capable of producing the various biological alterations generally attributed to endotoxins.Addendum. Since this report was submitted for publication preliminary tests of the effects of the typhosa lipopolysaccharide in man were undertaken(17). These indicate that when injected i.v. the minimum pyrogenic dose for a 70 kg subject lies in the range of.01-.04 μg.