Ex vivo effects of high-density lipoprotein exposure on the lipopolysaccharide-induced inflammatory response in patients with severe cirrhosis

Authors

  • Arnaud Galbois,

    1. INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Hôpital Beaujon, Clichy, France
    2. Université Denis Diderot-Paris 7, site Bichat, Paris, France
    3. Service d'Hépatologie, Hôpital Beaujon, Clichy, France
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  • Dominique Thabut,

    Corresponding author
    1. INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Hôpital Beaujon, Clichy, France
    2. Service d'Hépato-Gastroentérologie, Hôpital de la Pitié-Salpêtrière, Paris, France
    • INSERM, Hôpital Beaujon, 92118 CLICHY, France
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    • fax: 01 42161427

  • Khalid A. Tazi,

    1. INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Hôpital Beaujon, Clichy, France
    2. Université Denis Diderot-Paris 7, site Bichat, Paris, France
    3. Service d'Hépatologie, Hôpital Beaujon, Clichy, France
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  • Marika Rudler,

    1. INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Hôpital Beaujon, Clichy, France
    2. Université Denis Diderot-Paris 7, site Bichat, Paris, France
    3. Service d'Hépatologie, Hôpital Beaujon, Clichy, France
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  • Morvarid Shir Mohammadi,

    1. INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Hôpital Beaujon, Clichy, France
    2. Université Denis Diderot-Paris 7, site Bichat, Paris, France
    3. Service d'Hépatologie, Hôpital Beaujon, Clichy, France
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  • Dominique Bonnefont-Rousselot,

    1. Laboratoire des Lipides, Hópital de la Pitié-Salpêtrière, Paris, France
    2. Laboratoire de Biochimie Métabolique (EA 3617), Faculté de Pharmacie, Paris, France
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  • Hind Bennani,

    1. Service d'Immunologie et d'Hématologie, Hôpital Beaujon, Clichy, France
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  • Annie Bezeaud,

    1. Service d'Immunologie et d'Hématologie, Hôpital Beaujon, Clichy, France
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  • Zera Tellier,

    1. Laboratoire Français du Fractionnement et des Biotechnologies, Courtaboeuf, France
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  • Cécile Guichard,

    1. INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Hôpital Beaujon, Clichy, France
    2. Université Denis Diderot-Paris 7, site Bichat, Paris, France
    3. Service d'Hépatologie, Hôpital Beaujon, Clichy, France
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  • Nicolas Coant,

    1. Université Denis Diderot-Paris 7, site Bichat, Paris, France
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  • Eric Ogier-Denis,

    1. Université Denis Diderot-Paris 7, site Bichat, Paris, France
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  • Richard Moreau,

    1. INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Hôpital Beaujon, Clichy, France
    2. Université Denis Diderot-Paris 7, site Bichat, Paris, France
    3. Service d'Hépatologie, Hôpital Beaujon, Clichy, France
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    • These authors contributed equally to this work.

  • Didier Lebrec

    1. INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Hôpital Beaujon, Clichy, France
    2. Université Denis Diderot-Paris 7, site Bichat, Paris, France
    3. Service d'Hépatologie, Hôpital Beaujon, Clichy, France
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    • These authors contributed equally to this work.


  • Potential conflict of interest: Nothing to report.

Abstract

High-density lipoproteins (HDL) are known to neutralize lipopolysaccharide (LPS). Because patients with cirrhosis have lower HDL levels, this may contribute to LPS-induced ex vivo monocyte overproduction of proinflammatory cytokines. However, the effects of HDL on cytokine production by monocytes from patients with cirrhosis have never been studied. The aim of this study was to determine the effects of HDL on LPS-induced proinflammatory cytokine production in whole blood and isolated monocytes from patients with severe cirrhosis and controls. Plasma levels of HDL and cytokines were determined. The effects of reconstituted HDL (rHDL) on LPS-induced cytokine production in whole blood were assessed by cytokine array and on tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) production in isolated monocytes. Plasma HDL levels were significantly lower in patients with cirrhosis than in controls. Plasma levels of TNF-α and IL-6 were significantly higher in patients with cirrhosis than in controls. Incubation of rHDL with whole blood prevented LPS-induced TNF-α and IL-6 overproduction in patients with cirrhosis. LPS-induced TNF-α production and CD14 expression were significantly more marked in cirrhotic monocytes than in control monocytes, and both decreased significantly after rHDL incubation. LPS-induced down-regulation of scavenger receptor, class B, type I (SR-BI) expression was abolished in cirrhotic monocytes. Conclusions: This study shows that rHDL abolishes the LPS-induced overproduction of proinflammatory cytokines in whole blood from patients with severe cirrhosis. These results were confirmed in isolated monocytes from these patients. This suggests that administration of rHDL might be a useful strategy for the treatment of cirrhosis to limit LPS-induced cytokine overproduction. (HEPATOLOGY 2009;49:175-184.)

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