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

• Published in: Suez Canal University Medical Journal. Vol. 9; no. 2; pp. 171 - 180
• Main Authors: Ibrahim, Jihan H., Mahmud, Mushirah A., Kamil, Azzah, al-Serafi, Tahir I., Fawzi, Manal S.
• Format: Journal Article
• Language: Arabic; English
• Published: Ismailia, Egypt Suez Canal University, Faculty of Medicine 2006
• ISSN: 1110-6999; 2090-2581

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.