SummaryTriglyceride-rich lipoproteins bind and inactivate bacterial endotoxin in vitro and prevent death when given before a lethal dose of endotoxin in animals. However, lipoproteins have not yet been demonstrated to improve survival in polymicrobial gram-negative sepsis. We therefore tested the ability of triglyceride-rich lipoproteins to prevent death after cecal ligation and puncture (CLP) in rats. Animals were given bolus infusions of either chylomicrons (1 g triglyceride/kg per 4 h) or an equal volume of saline for 28 h after CLP. Chylomicron infusions significantly improved survival (measured at 96 h) compared with saline controls (80 vs 27%, P ~<0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 _+ 3 vs 136 __ 51 pg/ml, mean + SEM, P ~<0.03) and 6 h (121 +_ 54 vs 1,026 _+ 459 pg/ml, P ~<0.05) after CLP. The reduction in serum endotoxin correlated with a reduction in serum tumor necrosis factor, measured 6 h after CLP (0 +-0 vs 58 __. 24 pg/ml, P ~<0.03), suggesting that chylomicrons improve survival in this modal by limiting macrophage exposure to endotoxin and thereby reducing secretion of inflammatory cytokines. Infusions of a synthetic triglyceride-rich lipid emulsion (Intralipid; KabiVitrum, Inc., Alameda, CA) (1 g triglyceride/kg) also significantly improved survival compared with saline controls (71 vs 27%, P ~<0.03). These data demonstrate that triglyceriderich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis.

No abstract

No abstract