Quantitative Studies of Febrile Tolerance and Levels of Specific Antibody Evoked by Bacterial Endotoxin.

A series of endotoxin injections, either in constant or progressively increasing increments, will induce a state of refractoriness termed endotoxin tolerance. Resistance to the febrile effect of endotoxin is believed to be of short duration, disappearing within 3 weeks (2). Inasmuch as bacterial endotoxins are potent 0 antigens and give rise to the production of specific antibody, early workers considered the possibility of a correlation between increased antibody levels and diminished febrile response (3). However, Morgan was unable to discern a relationship between the magnitude of febrile reactivity and the levels of 0 agglutinins attained in rabbits given typhoid endotoxin (4). Subsequently, Beeson sought, without success, to transfer tolerance passively with serum of rabbits that had been rendered refractory (5). He also reported that the tolerant state was accompanied by increased activity of the reticuloendothelial system (RES). His finding that febrile tolerance was abolished by "blockade" of the RES with thorium dioxide (Thorotrast) attested to the major role of the RES in this situation (6). These findings constituted the major evidence in support of the concept that humoral mechanisms play no role in tolerance. Nonetheless, compelling data to the contrary had been obtained by Creech,