Observations on the pyrogenic response and its application to the bioassay of endotoxin.

Endotoxins prepared from gram-negative bacteria produce a wide variety of physiological reactions when administered to man and experimental animals. The intravenous injection of microgram quantities of these lipopolysaccharides into the appropriate host is followed by fever, leukopenia, thrombocytopenia, hyperglycemia, and irreversible shock. In addition, endotoxins are capable of producing the Shwartzman phenomenon, dermal necrosis, renal cortical necrosis, and hemorrhagic necrosis of certain tumors (1). The ubiquity of endotoxins has necessitated routine screening of all fluids and medications prepared for parenteral therapy, for which the pyrogenic response of the rabbit is commonly used. However, there have been few systematic studies of the dose-pyrogenic response relationships and little is known concerning the relative susceptibilities of rabbit and man to the pyrogenic and toxic properties of endotoxin (2-5). In this report the dose-febrile response curve for Serratia marcescens endotoxin is described. Data are also presented which show the relative susceptibilities of several species, including man, to the pyrogenic properties of endotoxin. An analysis of the data from an extensive series of experiments demonstrates that the febrile reaction of the rabbit provides a consistent and objective procedure for the bioassay of endotoxins.