INACTIVATION OF BACTERIAL EXOTOXINS AND ENDOTOXIN BY IRON

Abstract

Two mechanisms receiving widespread attention in studies on irreversibility in hemorrhagic shock[long dash]a derangement of iron metabolism, and the release of bacterial endotoxin[long dash]have usually been considered as unrelated entities. However, the increased susceptibility to bacterial endotoxins, which follows even brief episodes of hemorrhagic hypotension, may be due to the inhibiting action of hypoxia on the uptake of iron by reticuloendothelial (RE) cells, because of resultant depression of iron-dependent, RE detoxifying mechanisms. In vitro experiments were undertaken to study the detoxifying function of iron in more detail. After incubation of Escherichia coli endotoxin in ferrous sulfate, its lethal effects and tissue-necrotizing actions in rabbits were counteracted. Addition of chelating agents to iron-detoxified endotoxin resulted in partial recovery of lethal effectiveness. The in vitro inactivation of endotoxin by inorganic iron may be due to prior chelation, by iron, of metal-binding sites on the toxin molecule which normally attract other cations, in vivo. The observation of an in vitro inactivation of endotoxin by iron warrants the further investigation of the possible relationship between inactivation of endotoxin and storage iron in the RE system of shocked animals.