Format

Send to

Choose Destination
PLoS One. 2014 Dec 22;9(12):e112346. doi: 10.1371/journal.pone.0112346. eCollection 2014.

Normocaloric low cholesterol diet modulates Th17/Treg balance in patients with chronic hepatitis C virus infection.

Author information

1
Laboratory of Molecular Virology and Oncology, Francesco Balsano Foundation, Rome, Italy; Institute of Molecular Biology and Pathology, National Research Council, Rome, Italy.
2
Laboratory of Molecular Virology and Oncology, Francesco Balsano Foundation, Rome, Italy.
3
Predictive Medicine Unit, Sapienza University, Rome, Italy.
4
Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy.

Abstract

Hepatitis C virus (HCV) infection is associated with hepatic and extrahepatic manifestations, including immunological disorders. Chronic Hepatitis C (CHC) is often characterized by cholesterol and lipid metabolism alterations, leading to hepatic steatosis. Cholesterol metabolism, in fact, is crucial for the viral life cycle. Recent works described that a higher dietary cholesterol intake is associated with the progression of HCV-related liver disease. CHC patients have increased levels of T helper 17 (Th17)-cells, a lymphocytic population involved in the pathogenesis of liver inflammation and autoimmune hepatitis. The balance between Th17 and regulatory T (Treg) cells is crucial for chronic inflammation and autoimmunity. Th17-cell differentiation is deeply influenced by the activation LXRs, nuclear receptors modulating cholesterol homeostasis. Moreover, HCV may affect these nuclear receptors, and cholesterol metabolism, through both direct and indirect mechanisms. On these bases, we hypothesized that modulation of cholesterol levels through Normocaloric Low Cholesterol Diet (NLCD) may represent an innovative strategy to reduce the progression of HCV infection, through the modulation of peripheral Th17/Treg balance. To this end, we performed a pilot study to investigate whether a Normocaloric Low Cholesterol Diet may be able to modulate Th17/Treg balance in patients affected by chronic HCV infection. After 30 days of NLCD CHC patients showed a significant reduction in Th17 cells frequency, which correlated with strong reduction of IL-17 and IL-22 serum levels. At the same time, we appreciated an increase in the percentage of Treg cells, thus improving Treg/Th17 balance. Moreover, we observed an increased expression of LXRs and their target genes: SREBP-1c and ABCA-1. In conclusion, NLCD finely regulates Th17/Treg balance, improving immune system response in CHC patients. This study could pave the way for new treatments of CHC patients, suggesting that change in lifestyle could support the management of these patients, promoting well-being and possibly hindering disease progression.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02038387.

PMID:
25532016
PMCID:
PMC4273946
DOI:
10.1371/journal.pone.0112346
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center