Temperature responses of mice to Escherichia coli endotoxin.

SJL mice kept in a 23° environment and injected intravenously with endotoxin developed a marked hypothermia compared with animals given pyrogen-free saline (PFS). In contrast, giving endotoxin to SJL mice which had been “pre-conditioned” for 4 hr at 36° caused relative hyperthermia. Both responses were best observed at 1½ hr after injection. An endotoxin dose of 0·02 μg. was at the threshold of detectability in mice pre-conditioned at 36°, while with 23° animals, the threshold dose was 0·2 μg. Dose-response curves, with an index of precision (λ) of about 0·73, were obtained for mice in both environments, endotoxin doses of about 20 μg. being in the plateau regions of maximum responses. Mouse strains SWR/J and CMRL behaved similarly to SJL, but the temperature responses at both 23° and 36° were smaller. BALB/cJ and AKR/J mice showed a hyperthermic response to endotoxin at 36° but no hypothermia at 23°, while ST/bJ mice showed the converse pattern of hypothermia after endotoxin at 23° but no hyperthermia at 36°. Thus the strain of mouse is an important variable. We suggest that a hypothermia test in SJL mice may provide a simple and convenient bioassay procedure for endotoxin. Although its sensitivity is much less than the rabbit pyrogenicity test, it may be useful for the quantitative measurement of endotoxin activity of such preparations as typhoid, pertussis and cholera vaccines which are rich in endotoxin.