Host resistance to bacterial endotoxemia: mechanisms in endotoxin-tolerant animals.

Abstract

We designed this study to determine the contribution to host defense of the humoral detoxifying mechanism in endotoxin-tolerant animals. Compared with normal serum, sera from tolerant rabbits proved to be a much more potent medium for the detoxification of endotoxins. A fivefold increase in the activity of heat-stable, organophosphate-resistant esterase in tolerant serum was shown to be associated with the low-density lipoprotein fraction. The response of tolerant rabbits to challenge with endotoxin was immediate and was manifested by a sharp drop in ionized calcium in serum and a rapid formation of endotoxin-lipoprotein (esterase) complexes in the circulation. Tolerant rabbits were capable of effecting a rapid intravascular detoxification of endotoxin in spite of total occlusion of blood flow to the liver and spleen. These results clearly support the thesis that intravascular detoxification plays a dominant role in the increased resistance of tolerant animals to endotoxin.