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 alpha (TNF-alpha) production were determined. RESULTS: 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. 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.
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 rabbitlipopolysaccharide 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 alpha (TNF-alpha) production were determined. RESULTS: 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. 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.
Authors: D Pajkrt; J E Doran; F Koster; P G Lerch; B Arnet; T van der Poll; J W ten Cate; S J van Deventer Journal: J Exp Med Date: 1996-11-01 Impact factor: 14.307
Authors: Diana Schmerler; Sophie Neugebauer; Katrin Ludewig; Sibylle Bremer-Streck; Frank Martin Brunkhorst; Michael Kiehntopf Journal: J Lipid Res Date: 2012-05-11 Impact factor: 5.922