Mechanisms of endotoxin tolerance. IX. Effect of exchange transfusion.

Healthy New Zealand rabbits were injected iv with an LD-80 dose of E. coli endotoxin. Twenty minutes later, after removal of over 50% of the endotoxin by the RES, exchange transfusion was performed, accomplishing a rapid and sustained reduction in the level of endotoxemia simulating that seen in animals rendered highly tolerant by seven prior sublethal injections of toxin. Depite such reduction in endotoxemia, 96-hr mortality was only slightly, and not significantly reduced compared to sham exchanged controls (70 vs 83% respectively). Additional control studies indicated that exchange tranfusion per se did not enhance endotoxin mortality. The findings directly support the concept that endotoxin tolerance is based primarily upon enhanced RES resistance to endotoxin toxicity rather than upon enhanced RES clearance of circulating endotoxin.