Alcoholic hepatitis as a T-cell mediated disorder: an hypothesis.
BACKGROUND
The mechanism by which alcohol induces alcoholic hepatitis, the precursor lesion for cirrhosis, has never been elucidated. In particular, direct toxicity has not been proven. This article reviews the hypothesis that a primary target of chronic alcohol ingestion is the T lymphocyte. The lesion in the T lymphocyte is characterized by reduced baseline secretion of cytokines, including tumor necrosis factor-alpha; although characterized by an exaggerated release of cytokines when stimulated by polyclonal activators such as endotoxin. High concentrations of cytokines, especially tumor necrosis factor-alpha, within the liver induce necrosis/apoptosis of hepatocytes.


METHODS
Data supporting this hypothesis in rodent models are reviewed.


CONCLUSIONS
A strategic approach for testing this concept in man is defined.
Batey
R G
RG
Department of Gastroenterology, John Hunter Hospital, Newcastle, New South Wales, Australia.
Clancy
R L
RL
Pang
G T
GT
Cao
Q
Q
D000818:Animals; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000209:etiology* / Q000235:genetics; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000209:etiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha