RECONSTITUTED HIGH-DENSITY-LIPOPROTEIN INHIBITS PHYSIOLOGICAL AND TUMOR-NECROSIS-FACTOR-ALPHA RESPONSES TO LIPOPOLYSACCHARIDE IN RABBITS

Objective: To determine the effect of reconstituted human high density lipoprotein (rHDL) on physiologic and cytokine responses to infusion of lipopolysaccharide. Design: A blinded, randomized trial of three pr eparations of a purified human rHDL with apolipoprotein A-I-phosphatid yl choline-cholesterol molar ratios of 1:100:10, 1:150:10, and 1:200:0 and placebo in a rabbit lipopolysaccharide intravenous infusion model . Interventions: Groups of six New Zealand white rabbits received eith er placebo or one of the three human rHDL preparations above as a sing le, 75-mg/kg (apoliproprotein A-I equivalent) dose intravenously over 10 minutes ending 5 minutes before the start of a 3-hour infusion of l ipopolysaccharide. Main Outcome Measures: Mean arterial pressure, base excess, and plasma tumor necrosis factor alpha (TNF-alpha) production were determined. Results: The human rHDL suppressed TNF-alpha product ion with the products having the highest fraction of phosphatidyl chol ine producing the greatest suppression of TNF-alpha production. The hu man rHDL 1:200:0 group maintained a low, near-baseline TNF-alpha conce ntration and minimal decline in mean arterial pressure and base excess throughout the lipopolysaccharide infusion in contrast to the placebo group. Conclusion: Reconstituted human high density lipoprotein appea rs to be useful in inhibiting the physiologic effects and cytokine rel ease associated with endotoxemia and may provide adjunctive treatment for patients with gram-negative sepsis.