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Imbalanced intrahepatic cytokine expression of interferon-gamma, tumor necrosis factor-alpha, and interleukin-10 in patients with acute-on-chronic liver failure associated with hepatitis B virus infection.

AbstractGOALS:
This study attempts to determine expressions of intrahepatic proinflammatory and anti-inflammatory cytokines and their secreting immunocytes to evaluate their roles in the pathogenesis of acute-on-chronic liver failure (ACLF) in chronically hepatitis B virus (HBV)-infected patients.
BACKGROUND:
ACLF generally affects patients with established, compensated chronic liver diseases who develop an acute deterioration in liver function. In China, HBV-associated ACLF patients account for more than 80% of ACLF patients owing to a high prevalence of chronic HBV infection. Clinical observation showed that the deterioration of this disease may correlate with host immune responses, but related underlying mechanism remains largely unknown.
STUDY:
In situ expressions of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and their secreting CD4, CD8 T cells, and Kupffer cells (KCs) were analyzed in the livers of patients with ACLF, chronic hepatitis B (CHB), and normal controls (NC) using immunohistochemistry.
RESULTS:
Intrahepatic proinflammatory IFN-gamma and TNF-alpha expressions were markedly up-regulated in ACLF compared with CHB and NC. However, similar anti-inflammatory IL-10 expressions were observed in ACLF and CHB. IFN-gamma overexpression correlated significantly with increased CD4 and CD8 T-cell accumulation. TNF-alpha up-regulation also correlated significantly with increased KCs.
CONCLUSIONS:
The imbalanced expression of proinflammatory and anti-inflammatory cytokines and increased accumulation of CD4, CD8 T cells, and KCs may contribute to immunopathogenesis in HBV-infected ACLF.
AuthorsZhengsheng Zou, Baosen Li, Dongping Xu, Zheng Zhang, Jing-Min Zhao, Guangde Zhou, Yanling Sun, Lei Huang, Junliang Fu, Yongping Yang, Lei Jin, Wei Zhang, Jun Zhao, Ying Sun, Shaojie Xin, Fu-Sheng Wang
JournalJournal of clinical gastroenterology (J Clin Gastroenterol) Vol. 43 Issue 2 Pg. 182-90 (Feb 2009) ISSN: 1539-2031 [Electronic] United States
PMID18633332 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma
Topics
  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes (immunology)
  • CD8-Positive T-Lymphocytes (immunology)
  • Cytokines (metabolism)
  • Female
  • Hepatitis B virus (immunology, pathogenicity)
  • Hepatitis B, Chronic (immunology, physiopathology, virology)
  • Humans
  • Immunohistochemistry
  • Interferon-gamma (metabolism)
  • Interleukin-10 (metabolism)
  • Kupffer Cells (immunology)
  • Liver (cytology, immunology)
  • Liver Cirrhosis (immunology, physiopathology, virology)
  • Liver Failure, Acute (immunology, physiopathology, virology)
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Tumor Necrosis Factor-alpha (metabolism)
  • Up-Regulation

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