Enhanced apoptosis of peripheral blood mononuclear cells from chronic hcv patients is associated with reduced caspase 3 activity

Abstract EN

Background: Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease throughout the world.

Down-regulation of the immune response plays a major role in HCV persistence.

Recent investigations suggest that apoptosis of peripheral blood mononuclear cells (PBMCs) contributes to such down-regulation.

Objective: The current study investigates apoptotic changes in PBMCs and their relation to caspase-3 and -8 activities in patients with chronic HCV infection.

Methods: Apoptosis were investigated by measuring annexin-V binding using flowcytometry and DNA fragmentation using agarose gel electrophoresis, and caspases-3 and -8 specific activities were also measured in 43 chronic HCV patients and 10 normal control subjects.

Results: A significantly higher percent of annexin-V positive PBMCs was found in chronic HCV patients than controls (p<0.0001).

DNA fragmentation was detected in PBMCs from 20/43 patients (46.5%) but not from controls.

There was no statistically significant difference between HCV-PCR positive and negative patients as regards the degree of PBMCs apoptosis.

Caspase-3 activity was significantly lower in patients than controls (p=0.001), was significantly lower in HCV-PCR positive than controls (p=0.001) and was significantly higher in patients with PBMCs DNA fragmentation (p=0.005).

On the other hand, caspase-8 activity was comparable in both patients and control groups.

However, patients with PBMCs DNA fragmentation showed statistically significant higher activity than those without (p=0.023).

There was a statistically significant direct correlation between caspase-3 and caspase-8 activities in the patients group (r=0.56, pO.OOOl).

Conclusions: Chronic HCV infection is associated with PBMCs apoptosis irrespective of the presence of viremia.

However, this apoptosis is independent on activation of either caspase-3 or caspase-8.