Bioassay of endotoxin clearance in vivo and by perfused rat liver

Endotoxin clearances in vivo and by the isolated perfused rat liver were evaluated via bioassay in lead-sensitized rats. A linear relationship between the probit of shock lethality and the endotoxin dose in the probit range of 4-6 was validated. Endotoxin clearance in normal, fed rats displayed a linear relationship between the logarithm of the blood endotoxin concentration and time throughout the period of 15-240 min at doses of 500 and 1,000 mug/ rat; the half-time values were 58-63 min. Decreasing the endotoxin dose to 250 mug resulted in multiphasic clearance curves. Induction of tolerance to endotoxin resulted in marked acceleration of endotoxin clearance. Endotoxin clearance from the isolated perfused rat liver was not influenced by serum or rat blood as compared to clearance from a balanced salt solution. These data suggest that a physiologically stressful dose of endotoxin is slowly cleared from the blood and, therefore, circulates for prolonged periods.