Hypothesis: The intravenous administration of a protein free phospholipid rich emulsion is a safe and effective method for neutralizing the physiological effects of bacterial endotoxin.
Aims : The overall aim of the project is determine whether the lipid emulsion is capable of neutralizing bacterial endotoxin in human volunteers. This study will have two parts. Part 1, described in this application, is designed to provide pharmacokinetic and tolerability data. We also plan to study the remodeling of the emulsion into lipoproteins, the effect of the emulsion on the ability of LPS to generate TNF-alpha in vitro and the effects of the emulsion on CD 14 (endotoxin) receptors on blood monocytes. Part 2, to be submitted in a follow-up application, will determine the effects of administering phospholipid emulsion on endotoxin response in healthy human volunteers. Goals: This study is designed to determine: 1) Dosing levels and tolerability of the lipid emulsion. Specifically, the dose of emulsion required to safely raise plasma phospholipid to a level expected to neutralize the effects of endotoxin. 2) The remodeling of lipoproteins including cholesterol, triglyceride, phospholipids and apolipoprotiens as a consequence of infusion of phospholipid rich emulsion. 3) Effect of emulsion administration on the ability of LPS to generate TNF alpha in vitro using a whole blood system. 4) Effects of emulsion administration on expression of the CD14 endotoxin receptor on monocytes.
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