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February 1994

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

Author Affiliations

From the Department of Surgery, Medical College of Georgia, Augusta (Drs Cué, DiPiro, Blankenship, Mansberger, and Hawkins); the University of Georgia, College of Pharmacy, Athens (Dr DiPiro and Mr Brunner); and the Central Laboratory, Blood Transfusion Service, Swiss Red Cross, Bern, Switzerland (Dr Doran).

Arch Surg. 1994;129(2):193-197. doi:10.1001/archsurg.1994.01420260089012

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)