Cirrhosis and Liver Failure
Different changes in mitochondrial apoptotic pathway in lymphocytes and granulocytes in cirrhotic patients with sepsis
Article first published online: 17 APR 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 33, Issue 6, pages 834–842, July 2013
How to Cite
Liver Int. 2013: 33: 834–842
- Issue published online: 9 JUN 2013
- Article first published online: 17 APR 2013
- Accepted manuscript online: 16 MAR 2013 05:42PM EST
- Manuscript Accepted: 10 MAR 2013
- Manuscript Revised: 5 FEB 2013
- Manuscript Received: 26 JUL 2012
- bacterial infections;
Background & Aims
Apoptosis regulates leucocyte response during bacterial infections. This study explored leucocyte apoptotic pathway in cirrhotic patients with or without infections or sepsis.
In cirrhotic patients with bacterial infection or sepsis, the expression of Caspase 9, Bcl-2 family proteins, which comprises pro-apoptotic molecules, such as Bax, and anti-apoptotic molecules, such as Bcl-2 and Bcl-xL, were measured in peripheral lymphocytes and granulocytes. Regulatory microRNAs MIR-15 and MIR-16 were also measured.
This study enrolled 80 patients with cirrhosis, of whom 28 had no evidence of infections, 32 had bacterial infections and 20 had sepsis; reference values were obtained from 10 age-matched healthy subjects. An over-expression of Caspase-9 and pro-apoptotic protein Bax was found in lymphocytes of cirrhotic patients with infection or sepsis as compared with non-infected cases (P = 0.05 and 0.0001, respectively), while anti-apoptotic proteins Bcl-2 and Bcl-xL were downregulated. In granulocytes, lowest expression of pro-apoptotic protein Bax occurred in septic patients, while in cirrhotics with infections anti-apoptotic Bcl-2 and Bcl-xL were upregulated. Eight patients died; the survivors had less derangements in Bax, Bcl-2 and BcL-xL expression than non-survivors. The pro-apoptotic miRNA, MIR-15 and MIR-16, were upregulated in cirrhotics with bacterial infections.
Overall, the data show in lymphocytes, and not in granulocytes, an activation of the pro-apoptotic pathway in cirrhotic patients with bacterial infections, which correlates with the severity of the infection and the outcome.