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.
OBJECTIVE
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.


METHODS
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.
Zou
Zhengsheng
Z
Department of Severe Liver Diseases, Beijing 302 Hospital, Beijing Institute of Infectious Diseases, Beijing, China.
Li
Baosen
B
Xu
Dongping
D
Zhang
Zheng
Z
Zhao
Jing-Min
JM
Zhou
Guangde
G
Sun
Yanling
Y
Huang
Lei
L
Fu
Junliang
J
Yang
Yongping
Y
Jin
Lei
L
Zhang
Wei
W
Zhao
Jun
J
Sun
Ying
Y
Xin
Shaojie
S
Wang
Fu-Sheng
FS
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006515:Hepatitis B virus / Q000276:immunology / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007728:Kupffer Cells / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology; D008103:Liver Cirrhosis / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D017114:Liver Failure, Acute / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma