Reconstituted high density lipoprotein inhibits physiologic and tumor necrosis factor alpha responses to lipopolysaccharide in rabbits
J. I. Cue, J. T. DiPiro, L. J. Brunner, J. E. Doran, M. E. Blankenship, A. R. Mansberger and M. L. Hawkins
Department 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.
