The antipyretic effect of polymyxin B in endotoxin-induced fever

LPSS. typhimurium (0.3 g per kg) injected intravenously into conscious goats induced an inhibition of the extrinsic ruminal contractions in association with pyrexia and changes in heart rate. Pretreatment with polymyxin B (3 mg per kg i.v.) antagonized the endotoxin-induced symptoms in this species. In rabbits, the intravenous administration of LPSE. coli (0.1 g per kg) resulted in a febrile response, which could be markedly reduced by pretreatment with polymyxin B. Unlike endotoxins, the febrile response to leucocytic pyrogen was not inhibited after pretreatment with this antibiotic. Moreover, polymyxin B caused only a minimal decline in the febrile response due to sodium nucleinate from yeast (10 mg per kg). These results strengthen the view that the antipyretic activity of polymyxin B is due to an interaction of this cationic macromolecule with the anionic endotoxin molecule.