Increased bactericidal/permeability increasing protein in patients with cirrhosis

Liver Int. 2010 Jan;30(1):94-101. doi: 10.1111/j.1478-3231.2009.02121.x. Epub 2009 Sep 18.


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.

Aims: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimicrobial Cationic Peptides / blood*
  • Antimicrobial Cationic Peptides / genetics
  • Blood Proteins / genetics
  • Carrier Proteins
  • Cells, Cultured
  • Female
  • Gene Expression
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Lipopolysaccharide Receptors / blood
  • Lipopolysaccharides / pharmacology
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology
  • Male
  • Membrane Glycoproteins
  • Middle Aged
  • Neutrophils / chemistry
  • Neutrophils / metabolism*
  • Neutrophils / pathology
  • RNA, Messenger / analysis
  • Tumor Necrosis Factor-alpha / blood


  • Acute-Phase Proteins
  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Carrier Proteins
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • bactericidal permeability increasing protein
  • lipopolysaccharide-binding protein