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Reconstituted high density lipoprotein inhibits physiologic and tumor necrosis factor alpha responses to
J I Cué1, J T DiPiro, L J Brunner
1Department of Surgery, Medical College of Georgia, Augusta.
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.