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

Abstract

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 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. Interventions: 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. Main Outcome Measures: Mean arterial pressure, base excess, and plasma tumor necrosis factor α (TNF-α) production were determined. Results: The human rHDL suppressed TNF-α production with the products having the highest fraction of phosphatidyl choline producing the greatest suppression of TNF-α production. The human rHDL 1:200:0 group maintained a low, near-baseline TNF-α concentration 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 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. (Arch Surg. 1994;129:193-197)