Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement

Authors

  • Agustín Albillos,

    Corresponding author
    1. Servicio de Gastroenterología, Hospital Ramón y Cajal, Alcalá de Henares, Madrid, Spain
    2. Laboratorio de Enfermedades del Sistema Inmune y Oncología, Unidad I+D Asociada al CSIC, Alcalá de Henares, Madrid, Spain
    3. Departamento de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
    • Dept. de Medicina, Facultad de Medicina-Campus Universitario, Universidad Alcalá, Ctra. Madrid-Barcelona km. 33.600, 28871 Alcalá de Henares, Madrid, Spain. Fax: (34) 91-3368085
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  • Antonio de la Hera,

    1. Laboratorio de Enfermedades del Sistema Inmune y Oncología, Unidad I+D Asociada al CSIC, Alcalá de Henares, Madrid, Spain
    2. Departamento de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
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  • Mónica González,

    1. Servicio de Gastroenterología, Hospital Ramón y Cajal, Alcalá de Henares, Madrid, Spain
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  • Jose-Luis Moya,

    1. Departamento de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
    2. Servicio de Cardiología, Hospital Ramón y Cajal, Alcalá de Henares, Madrid, Spain
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  • Jose-Luis Calleja,

    1. Servicio de Gastroenterología, Clinica Puerta de Hierro, Alcalá de Henares, Madrid, Spain
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  • Jorge Monserrat,

    1. Laboratorio de Enfermedades del Sistema Inmune y Oncología, Unidad I+D Asociada al CSIC, Alcalá de Henares, Madrid, Spain
    2. Departamento de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
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  • Luis Ruiz-del-Arbol,

    1. Servicio de Gastroenterología, Hospital Ramón y Cajal, Alcalá de Henares, Madrid, Spain
    2. Departamento de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
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  • Melchor Alvarez-Mon

    1. Laboratorio de Enfermedades del Sistema Inmune y Oncología, Unidad I+D Asociada al CSIC, Alcalá de Henares, Madrid, Spain
    2. Departamento de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
    3. Servicio de Enfermedades del Sistema Inmune y Oncología, Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
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Abstract

Intestinal bacterial overgrowth and translocation, both common in cirrhosis with ascites, may lead to the activation of monocytes and lymphocytes, increased levels of proinflammatory cytokines, and enhanced synthesis of nitric oxide present in cirrhosis. Bacterial endotoxin promotes the synthesis of lipopolysaccharide (LPS)-binding protein (LBP), and forms a LPS-LBP complex that binds to CD14. This study was designed to evaluate LBP levels and their correlation to the immune response and the hemodynamic status in cirrhotic patients. Plasma LBP, endotoxin, soluble CD14 (sCD14), cytokines, renin, nitrites, and systemic vascular resistance were determined before and 4 weeks after norfloxacin or placebo in 102 cirrhotic patients and 30 controls. LBP was elevated in 42% of ascitic cirrhotic patients (15.7 ± 0.7 versus 6.06 ± 0.5 μg/mL, P < .01). In 60% of high LBP patients, endotoxin was within normal range. Among ascitic patients, those with high LBP showed greater (P < .05) levels of sCD14, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), nitrites + nitrates (NOx)/creatinine, and renin, and lower vascular resistance. In the cirrhotic patients with high LBP, norfloxacin normalized (P < .01) LBP (from 16.6 ± 0.5 to 5.82 ± 0.8 μ g/mL) and sCD14; reduced the level of cytokines, NOx/creatinine, and renin; and increased vascular resistance; but lacked effect in patients with normal LBP. Portal pressure was unchanged after norfloxacin in another group of 18 cirrhotic patients with high and 19 with normal LBP. In conclusion, the subset of ascitic cirrhotic patients with marked immune and hemodynamic derangement is identified by increased LBP levels. Amelioration of these abnormalities by norfloxacin suggests the involvement of enteric bacteria or their products in the triggering of the process.

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