Triglyceride-rich lipoproteins bind and inactive 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 < or = 0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 +/- 3 vs 136 +/- 51 pg/ml, mean +/- SEM, P < or = 0.03) and 6 h (121 +/- 54 vs 1,026 +/- 459 pg/ml, P < or = 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 < or = 0.03), suggesting that chylomicrons improve survival in this model 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 < or = 0.03). These data demonstrate that triglyceride-rich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis.
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July 01 1995
Triglyceride-rich lipoproteins prevent septic death in rats.
T E Read,
T E Read
Department of Surgery, University of California, San Francisco 94143, USA.
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C Grunfeld,
C Grunfeld
Department of Surgery, University of California, San Francisco 94143, USA.
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Z L Kumwenda,
Z L Kumwenda
Department of Surgery, University of California, San Francisco 94143, USA.
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M C Calhoun,
M C Calhoun
Department of Surgery, University of California, San Francisco 94143, USA.
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J P Kane,
J P Kane
Department of Surgery, University of California, San Francisco 94143, USA.
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K R Feingold,
K R Feingold
Department of Surgery, University of California, San Francisco 94143, USA.
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J H Rapp
J H Rapp
Department of Surgery, University of California, San Francisco 94143, USA.
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T E Read
Department of Surgery, University of California, San Francisco 94143, USA.
C Grunfeld
Department of Surgery, University of California, San Francisco 94143, USA.
Z L Kumwenda
Department of Surgery, University of California, San Francisco 94143, USA.
M C Calhoun
Department of Surgery, University of California, San Francisco 94143, USA.
J P Kane
Department of Surgery, University of California, San Francisco 94143, USA.
K R Feingold
Department of Surgery, University of California, San Francisco 94143, USA.
J H Rapp
Department of Surgery, University of California, San Francisco 94143, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 182 (1): 267–272.
Citation
T E Read, C Grunfeld, Z L Kumwenda, M C Calhoun, J P Kane, K R Feingold, J H Rapp; Triglyceride-rich lipoproteins prevent septic death in rats.. J Exp Med 1 July 1995; 182 (1): 267–272. doi: https://doi.org/10.1084/jem.182.1.267
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