A RECONSTITUTED, APOLIPOPROTEIN-A-I CONTAINING LIPOPROTEIN REDUCES TUMOR-NECROSIS-FACTOR RELEASE AND ATTENUATES SHOCK IN ENDOTOXEMIC RABBITS

A reconstituted lipoprotein, containing human apolipoprotein A-1 and p hosphatidylcholine (1:200, molar ratio), referred to as ApoLipo, was u sed prophylactically in an endotoxin shock model in anesthetized rabbi ts. ApoLipo was administered at a dose of 75 mg protein/kg body weight 15 min before the beginning of a slow, continuous lipopolysaccharide (LPS, endotoxin) infusion (4.17 mug LPS/kg/hr). During the 6 hr LPS in fusion, the Control-LPS group manifested a marked increase in serum tu mor necrosis factor (TNF, peak value 7.82 [2.7-11.2] ng/ml at 1 hr), a nd many of the pathophysiologic sequelae of endotoxin shock, including hypotension (MAP: 59 +/- 7 mmHg) and metabolic acidosis (BE: -9.9 +/- 2.7) at 3 hr, and a severe neutropenia developed rapidly (PMN count: 5 +/- 3% of baseline at 30 min). In the ApoLipo treated group, serum T NF levels did not rise during the course of LPS infusion (0.1 [0.06-0. 64] ng/ml at 1 hr). Hypotension (77 +/- 2 mmHg) and acidosis (-2.7 +/- 0.4) were also significantly attenuated, and the appearance of leukop enia was delayed by 1 hr (110 +/- 12% at 30 min, but 9 +/- 2% at 2 hr) . Endotoxemia in the ApoLipo treated group was reduced in comparison t o controls, albeit nonsignificantly. The infusion of the same dose of phosphatidylcholine without apoA-I was significantly less efficacious.