EFFECT OF HYPERTRIGLYCERIDEMIA ON ENDOTOXIN RESPONSIVENESS IN HUMANS

Triglyceride-rich lipoproteins can inhibit endotoxin activity in vitro and in rodents. We sought to determine whether Intralipid, a triglyce ride-rich fat emulsion which in contact with plasma functions similarl y to endogenous lipoproteins, can alter the human response to endotoxi n, Intralipid inhibited endotoxin-induced cytokine production in human whole blood in vitro in a dose-dependent manner, with maximal inhibit ion (up to 70%) being achieved at a concentration of 10 g/liter. In he althy men, a bolus intravenous injection of endotoxin (lot EC-5; 20 U/ kg of body weight) was given midway through a 4-h infusion (125 ml/h) of either 5% glucose (n = 5) or 20% Intralipid (n = 5). The infusion o f Intralipid led to an increase in triglyceride levels in serum from 9 5 +/- 16 to 818 +/- 135 mg/dl prior to endotoxin administration, i.e., levels that importantly reduced cytokine production in endotoxin-stim ulated whole blood. However, in vivo hyp ertriglyceridemia did not inf luence inflammatory responses to endotoxin (fever, release of tumor ne crosis factor and soluble tumor necrosis factor receptors, and leukocy tosis) or even potentiated endotoxin responses (release of interleukin s 6 and 8 and neutrophil degranulation). Hypertrigiyceridemia does not inhibit the in vivo responses to endotoxin in humans.