Further studies on the antipyretic action of polymyxin B in pyrogen-induced fever.

A study of the antipyretic effect of polymyxin B was undertaken to determine how this agent reduces fever in rabbits. It involved the effects of the drug: (1) on fever induced by exogenous pyrogenes (E. coli lipopolysaccharide, synthetic double-stranded ribonucleic acid, sodium nucleinate from yeast) and leucocytic pyrogen, (2) on the release of endogenous pyrogen in vivo and in vitro, and (3) on leucocytic and exogenous pyrogens in vitro. The results indicate that polymyxin B produces an antipyretic effect in endotoxin-induced fever primarily by an interaction of this cationic macromolecule with the anionic endotoxin molecule. Further it is likely that polymyxin B inhibits endogenous pyrogen synthesis and/or release from polymorphonuclear leucocytes.