title: Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement.
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 microg/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 alpha (TNF-alpha), 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 microg/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.
authors.affiliation: Servicio de Gastroenterología, Hospital Ramón y Cajal, Alcalá de Henares, Madrid, Spain. aalbillosm@meditex.es
authors.forename: Agustín
authors.initials: A
authors.lastname: Albillos
authors.forename: Antonio
authors.initials: A
authors.lastname: de la Hera
authors.forename: Mónica
authors.initials: M
authors.lastname: González
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Moya
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Calleja
authors.forename: Jorge
authors.initials: J
authors.lastname: Monserrat
authors.forename: Luis
authors.initials: L
authors.lastname: Ruiz-del-Arbol
authors.forename: Melchor
authors.initials: M
authors.lastname: Alvarez-Mon
mesh_terms: D000209:Acute-Phase Proteins; D000890:Anti-Infective Agents / Q000008:administration & dosage; D015703:Antigens, CD / Q000097:blood; D001201:Ascites / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000276:immunology; D002352:Carrier Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007422:Intestines / Q000382:microbiology; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009643:Norfloxacin / Q000008:administration & dosage; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D012995:Solubility; D013152:Splanchnic Circulation / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects / Q000276:immunology; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D000890:Anti-Infective Agents; D015703:Antigens, CD; D002352:Carrier Proteins; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009643:Norfloxacin; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein