Lipoproteins can bind lipopolysaccharide (LPS) and decrease the LPS-stimulated production of pro-inflammatory cytokines. We investigated the effect of increased plasma concentrations of low-density-lipoproteins (LDL) on survival and cytokine production after a lethal challenge with either LPS or live Gram-negative bacteria in LDL receptor deficient mice (LDLR-/-). The LDLR-/- mice challenged with LPS had an eightfold increased LD50 when compared with the wild type controls (C57Bl/6J), while tumor necrosis factor alpha (TNFalpha) and interleukin-1 alpha (IL-1 alpha) plasma concentrations were decreased twofold. LDLR-/- mice had significantly lower and delayed mortality than control mice after infection with Klebsiella pneumoniae. No differences in the outgrowth of bacteria in the organs were present between the two groups, while circulating cytokine concentrations were decreased twofold in LDLR-/- mice. In contrast, the LPS-stimulated in vitro production of cytokines by peritoneal macrophages of LDLR-/- mice was significantly increased compared with controls. This increase was associated with enhanced specific binding of LPS to the macrophages of LDLR-/- mice. In conclusion, endogenous LDL can protect against the lethal effects of endotoxin and Gram-negative infection. At least part of this protection is achieved through decreased in vivo production of pro-inflammatory cytokines, in spite of increased cytokine production capacity.
M G Netea, P N Demacker, B J Kullberg, O C Boerman, I Verschueren, A F Stalenhoef, J W van der Meer
Title and authors | Publication | Year |
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NOD2 and toll-like receptors are nonredundant recognition systems of Mycobacterium tuberculosis
G Ferwerda, SE Girardin, BJ Kullberg, LL Bourhis, DJ de Jong, DM Langenberg, R Crevel, GJ Adema, TH Ottenhoff, JW van der Meer, MG Netea |
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Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis*
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High levels of C-reactive protein with low total cholesterol concentrations additively predict all-cause mortality in patients with coronary artery disease
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Low-Density Lipoprotein Cholesterol: Association with Mortality and Hospitalization in Hemodialysis Patients
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Serum lipids and disease severity in children with severe meningococcal sepsis*
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Critical Care Medicine | 2005 |
Effect of recombinant murine granulocyte colony-stimulating factor with or without fluoroquinolone therapy on mixed-infection abscesses in mice
LE Stearne, AG Vonk, BJ Kullberg, IC Gyssens |
Antimicrobial agents and chemotherapy | 2005 |
Apolipoproteins modulate the inflammatory response to lipopolysaccharide
JF Berbee, LM Havekes, PC Rensen |
Journal of Endotoxin Research | 2005 |
Neuronal, Endocrine, and Anorexic Responses to the T-Cell Superantigen Staphylococcal Enterotoxin A: Dependence on Tumor Necrosis Factor-
A Rossi-George |
The Journal of neuroscience : the official journal of the Society for Neuroscience | 2005 |
Differential Cytokine Production and Toll-Like Receptor Signaling Pathways by Candida albicans Blastoconidia and Hyphae
CA van der Graaf, MG Netea, I Verschueren, JW van der Meer, BJ Kullberg |
Infection and immunity | 2005 |
Nucleotide-Binding Oligomerization Domain-2 Modulates Specific TLR Pathways for the Induction of Cytokine Release
MG Netea, G Ferwerda, DJ de Jong, T Jansen, L Jacobs, M Kramer, TH Naber, JP Drenth, SE Girardin, BJ Kullberg, GJ Adema, JW der Meer |
Journal of immunology (Baltimore, Md. : 1950) | 2005 |