Reconstituted High Density Lipoprotein Inhibits Physiologic and Tumor Necrosis Factor α Responses to Lipopolysaccharide in Rabbits

Abstract

To determine the effect of reconstituted human high density lipoprotein (rHDL) on physiologic and cytokine responses to infusion of lipopolysaccharide. A blinded, randomized trial of three preparations of a purified human rHDL with apolipoprotein A-I-phosphatidyl choline-cholesterol molar ratios of 1:100:10, 1:150:10, and 1:200:0 and placebo in a rabbit lipopolysaccharide intravenous infusion model. Groups of six New Zealand white rabbits received either placebo or one of the three human rHDL preparations above as a single, 75-mg/kg (apolipoprotein A-I equivalent) dose intravenously over 10 minutes ending 5 minutes before the start of a 3-hour infusion of lipopolysaccharide. Mean arterial pressure, base excess, and plasma tumor necrosis factor alpha (TNF-alpha) production were determined. The human rHDL suppressed TNF-alpha production with the products having the highest fraction of phosphatidyl choline producing the greatest suppression of TNF-alpha production. The human rHDL 1:200:0 group maintained a low, near-baseline TNF-alpha concentration and minimal decline in mean arterial pressure and base excess throughout the lipopolysaccharide infusion in contrast to the placebo group. Reconstituted human high density lipoprotein appears to be useful in inhibiting the physiologic effects and cytokine release associated with endotoxemia and may provide adjunctive treatment for patients with gram-negative sepsis.