Neutralization of the Shwartzman Reactions by Polymyxin B

Summary Polymyxin B prevented the localized Shwartzman reaction in rabbits when admixed with the intravenous (i.v.) provocative dose of endotoxin but enhanced the reaction when admixed with the intracutaneous preparatory dose. Polymyxin B prevented the generalized Shwartzman reaction when admixed with either the preparatory or the provocative i.v. dose of endotoxin. A preparatory i.v. dose of endotoxin resulted in the production of low concentrations of plasma heparin-precipitable protein, and following a second or provocative dose of endotoxin 24 hrs later the concentration was augmented 30-fold. This augmentation was prevented by polymyxin B admixed with the provocative but not with the preparatory dose of endotoxin. These data indicate that the production of high concentrations of heparin-precipitable protein is not in itself sufficient for the production of the generalized Shwartzman reaction. The addition of polymyxin B in vitro to heparinized plasma samples obtained after two i.v. doses of endotoxin did not depress the formation of heparin-precipitable protein. The admixture of polymyxin B to a single i.v. dose of endotoxin resulted in the reduction of the toxin mortality in rabbits from 23% to 4%.