Relation of pyrogenic and emetic properties of enterobacteriaceal endotoxin and of staphylococcal enterotoxin

The specificity of the first or "presumptive" portion of the U.S.P. rabbit pyrogen test was investigated employing a new absolute standard of reference. The reference standard was 0.9 per cent sodium chloride solution prepared to be pyrogen free. Details of the preparation were described. The hypothesis was explored that the temperature response of rabbits following iv injection of the standard solution was independent of exogenous pyrogen. Reactions observed among the rabbits in our colony allowed a classification of these animals ranging form "consistently reliable" to consistently unreliable." Details of the experimental results and implications for pyrogen testing were discussed. The recommendation has been made that all rabbit test animals be "screened" before pyrogen testing. In addition to this work, bacterial substances that elicit fever and vomiting were studies by means of the pyrogen test. The term endotoxin is commonly employed to describe the fever inducing substances of gram-negative bacilli. These pyrogenic substances, when isolated in either a relatively impure or purified state, are both pyrogenic in rabbits and cats as well as emetigenic in cats in microgram amounts. Enterotoxin is the term employed to characterize the emetic substance elaborated during the growth of some, but not, all, strains of Staphylococcus aureus. The most significant apparent action of the toxin on susceptible animals is to induce vomiting. However, another characteristic of this enterotoxin, which is sometimes overlooked, is to reduce fever. The hypothesis was formulated that the pyrexic component of enterotoxin was associated with the staphylococcus in the same manner that endotoxin was associated with certain gram-negative bacilli; that is, that the protein was a significant component of the cell itself which was released to the medium largely as a result of autolysis. Employing similar methods for preparation of endotoxin from known enterotoxic strains of S. aureus has yield preparation with less than one hundredth the activity of the enterobacteriaceal material, However, a purified enterotoxin material, with protein like rather than polysaccharide-like properties, has been found to be both pyrogenic and emetigenic in micrograms amounts. These results suggested that the emetigenic in microgram amounts. These results suggested that the enterobacteriaceal pyrogen-emetic substance(s) was a significant part of the whole cell, whereas the staphylococcal enterotoxin was elaborated as a metabolic product which apparently did not accumulate in the whole cell.