MECHANISMS OF ENDOTOXIN TOLERANCE

Open Access
Publisher Website
Google Scholar
Abstract
The mechanisms underlying the pyrogenic refractory state which develops rapidly during a continuous intravenous infusion of bacterial endotoxin have been further explored. The findings demonstrate that: (a) rabbits rendered refractory to a continuous intravenous infusion of E. coli endotoxin at a standard rate (18 x 10–4 µg/min) become highly refractory to a single intravenous test bolus of endotoxin, but remain fully responsive to preformed endogenous pyrogen and to substances known to release endogenous pyrogen, i.e. influenza virus, old tuberculin in specifically sensitized rabbits, and staphylococcal enterotoxin; (b) administration of fresh whole blood from normal donors containing an average of 1.6 – 108 granulocytes fails to restore febrile responsiveness to the continuing E. coli endotoxin infusion; (c) refractory phase plasma and liver homogenates exhibit no enhanced capacity to inactivate E. coli endotoxin pyrogenicity; (d) splenectomized animals readily develop the pyrogenic refractory state during E. coli endotoxin infusions and exhibit diminished, rather than the increased inflammatory responses to intradermal endotoxin seen in sham-operated controls; (e) continuous intravenous infusions of gelatin-stabilized, heat-killed pneumococci produce sustained fevers; and (f) continuous intravenous infusions of old tuberculin into specifically sensitized animals rapidly elicit a pyrogenic refractory state.

This publication has 27 references indexed in Scilit: