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.

Abstract

GOALS:

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.

• Authors: Zhengsheng 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
• Journal: Journal of clinical gastroenterology (J Clin Gastroenterol) Vol. 43 Issue 2 Pg. 182-90 (Feb 2009) ISSN: 1539-2031 [Electronic] United States
• PMID: 18633332 (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