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Neutralization of the Shwartzman Reactions by Polymyxin B¹

From the Departments of Medicine and Pathology, University of Colorado Medical Center, Denver, Colorado

Abstract

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%.

Footnotes

This work was supported by a grant from The John A. Hartford Foundation, New York, New York.

² Present Address, Department of Microbiology, The University of Arizona College of Medicine, Tucson, Arizona.