Increased bactericidal/permeability increasing protein in patients with cirrhosis

Abstract

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