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.

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.
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.
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.
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.
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
  • 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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