CHYLOMICRONS ENHANCE ENDOTOXIN EXCRETION IN BILE

Chylomicrons prevent endotoxin toxicity and increase endotoxin uptake by hepatocytes. As a consequence, less endotoxin is available to activ ate macrophages, thereby reducing tumor necrosis factor secretion. To determine whether the chylomicron-mediated increase in hepatocellular uptake of endotoxin results in increased endotoxin excretion into bile , we examined bile after endotoxin administration. A sublethal dose (7 mug/kg) of I-125-endotoxin was incubated with either rat mesenteric l ymph containing nascent chylomicrons (500 mg of chylomicron triglyceri de per kg of body weight) or an equal volume of normal saline (control s) for 3 h and then infused into male Sprague-Dawley rats. Bile sample s were collected via a common bile duct catheter for 24 h. Infusion of endotoxin incubated with chylomicrons increased biliary excretion of endotoxin by 67% at 3 h (P less-than-or-equal-to 0.006) and by 20% at 24 h (P less-than-or-equal-to 0.01) compared with infusion of endotoxi n incubated in saline. Endotoxin activity, as measured by the Limulus assay, was not detected in the bile of test animals. However, endotoxi n activity was detected after hot phenol-water extraction of bile, dem onstrating that endotoxin is inactive in the presence of bile but reta ins bioactivity after hepatic processing. Since the majority of an int ravenous endotoxin load has been shown to be cleared by the liver, acc eleration of hepatocyte clearance and biliary excretion of endotoxin m ay represent a component of the mechanism by which chylomicrons protec t against endotoxin-induced lethality.