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Chronic Alcohol Consumption Impairs Immune Response to HCV

It is well known that heavy alcohol (ethanol) consumption can cause progressive liver disease, and among individuals with hepatitis C, it is also associated with poorer response to interferon-based therapy.

In a study reported in the February 2007 issue of Gastroenterology, researchers analyzed the effect of ethanol on HCV-specific immune responses in mice, focusing on dendritic cells (DCs) as a mechanism for reduced CD8 cytotoxic T-lymphocyte (CTL) activity in response to the HCV NS5 non-structural protein.

Mice were fed an ethanol-containing or normal control diet for 8 weeks. DCs were then isolated from the spleen and evaluated for endocytosis properties, cell surface markers, allostimulatory activity, and cytokine production.

Results

Long-term ethanol exposure resulted in a reduced number of DCs in the spleen, but did not alter the cells' endocytosis capacity.

The myeloid population of DC cells was increased, while the lymphoid DC population was reduced.

Ethanol reduced expression of CD40 and CD86 co-stimulatory molecules on resting DCs, which was corrected following stimulation with lipopolysaccharide or poly I:C.

DCs in the ethanol-exposed mice had impaired allostimulatory activity.

Cytokine profiles of DCs isolated from ethanol-exposed mice demonstrated:

- enhanced interleukin (IL)-1-beta and IL-10 secretion;
- decreased tumor necrosis factor (TNF) alpha production;
- decreased IL-12 and IL-6 secretion;
- reduced interferon gamma production.

Impaired CTL responses to NS5 were corrected by introducing DCs from the control mice.


Conclusion

In conclusion, the authors wrote, "Altered DC function is one of the major changes induced by long-term ethanol consumption, which subsequently impairs the cellular immune response necessary for viral clearance."

Liver Research Center, Rhode Island Hospital and Brown Medical School, Providence, RI.

03/30/07

References
C Aloman, S Gehring, P Wintermeyer, and others. Chronic Ethanol Consumption Impairs Cellular Immune Responses Against HCV NS5 Protein Due to Dendritic Cell Dysfunction. Gastroenterology 132(2): 698-708. February 2007.

 


 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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