Increased bactericidal/permeability increasing protein in patients with cirrhosis.
BACKGROUND
High levels of endotoxin in patients with cirrhosis are thought to be responsible for the activation of tumour necrosis factor-alpha (TNF)-alpha-mediated pro-inflammatory pathways involved in haemodynamic alterations. Bactericidal/permeability increasing protein (BPI) is a protein found in neutrophils with endotoxin-binding and neutralization capacity. It is not known whether defective BPI production or release is present in cirrhosis.


OBJECTIVE
We investigated the levels of BPI in cirrhotic patients and its relation to other endotoxin-binding proteins and inflammatory markers.


METHODS
Plasmatic levels of BPI, lipopolysaccharide-binding protein, soluble CD14, TNF-alpha and BPI mRNA expression in neutrophils were determined in 130 patients and 30 healthy controls. The capacity of patients' plasma to inhibit lipopolysaccharide (LPS)-mediated TNF-alpha production by monocytes from healthy donors was assessed in vitro.


RESULTS
Patients with cirrhosis exhibited an increase in BPI mRNA and plasma level of BPI when compared with healthy controls (P<0.05). Child C group displayed the highest frequency of patients with a high concentration of BPI. A positive correlation was found between TNF-alpha and plasma levels of BPI (P<0.01). High levels of BPI in plasma were able to significantly reduce in vitro TNF-alpha release by monocytes after a challenge with LPS (8.54 +/- 1.04 vs. 10.44 +/- 0.85 pg/ml, P=0.028).


CONCLUSIONS
BPI is increased in cirrhotic patients, especially in those with more severe liver disease. The amount of BPI in the plasma correlated with the TNF-alpha level and was able to reduce LPS-mediated TNF production by monocytes. BPI possibly plays a regulatory role by antagonizing the pro-inflammatory mechanisms mediated by TNF-alpha.
Guerra-Ruiz
Armando
A
Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain. r-gruiz@hotmail.com
Casafont
Fernando
F
Cobo
Marta
M
Terán
Alvaro
A
de-la-Peña
Joaquín
J
Estebanez
Angel
A
Pons-Romero
Fernando
F
D000209:Acute-Phase Proteins; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000097:blood* / Q000235:genetics; D001798:Blood Proteins / Q000235:genetics; D002352:Carrier Proteins; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C021623:bactericidal permeability increasing protein