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-α (TNF)-α-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-α 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-α 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-α and plasma levels of BPI (P<0.01). High levels of BPI in plasma were able to significantly reduce in vitro TNF-α 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-α 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-α.