Assay of endotoxin by the hypothermic response of mice

Abstract

Escherichia coli endotoxin injected into CMRL mice in a 23° environment produced a fall in rectal temperature at 3 hr post-injection. Endotoxin given i.v. produced a greater hypothermia than if injected i.p. Pretreatment of the mice with pertussis vaccine, BCG or Corynebacterium parvum substantially increased their responsiveness to endotoxin. SJL mice were more sensitive to endotoxin than CMRL mice and showed hypothermias as great as -4·9°. Endotoxins from Salmonella typhi and Bordetella pertussis had a similar activity to Esch. coli endotoxin, but Shigella flexneri was less active. There was no evidence to support the idea that endotoxin responsiveness depends on the mice having previous environmental exposure to the corresponding bacterium e.g. in the gut flora. The relative endotoxic activities of 1 batch each of pertussis, TAB and cholera vaccines were assayed by the hypothermias produced in SJL mice. Cholera vaccine was twice as potent as TAB which was 4 times more active than pertussis. The index of precision of the mouse hypothermia test (0·32-0·65) is not inferior to that of the standard rabbit pyrogenicity test (about 0·6). The test should be useful for comparing the endotoxic activities of preparations such as bacterial vaccines which may be rich in endotoxin.