Document Detail


Altered T-lymphocyte responsiveness to polyclonal cell activators is responsible for liver cell necrosis in alcohol-fed rats.
MedLine Citation:
PMID:  9622456     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The role of T-cell activation in alcoholic liver disease was investigated in rats fed alcohol and subsequently exposed to concanavalin A (Con A). Following Con A injection (20 mg/kg body weight), greater increases in liver-to-body weight ratio and ALT levels were observed at 12 and 24 hr in rats fed ethanol, compared with control rats fed sucrose. Furthermore, increases in serum interleukin-6 and tumor necrosis factor-alpha levels were noted in ethanol-fed rats, with maximal levels detected at 4 hr declining thereafter, but remaining above control levels at 24 hr. Analysis of T-cell subpopulations showed an increased percentage of CD4+, CD5+, and CD8+ T cells in blood from all groups, but not in liver perfusate. In contrast, a significant increase in the percentage of activated CD25+ T cells was detected in both blood and liver perfusate from rats fed ethanol even 24 hr after Con A injection. When CD4+ and CD8+ T cells from liver perfusate were cultured in the absence or presence of Con A, an increase in interleukin-6 and tumor necrosis factor-alpha production in supernatants was observed in ethanol-fed rats. In cultures stimulated with Con A, a 2- to 8-fold increase in cytokine production was detected, with intrahepatic CD4+ T cells being the major source. Immunohistological analysis revealed infiltration of CD4+ T cells around portal vein and central vein areas associated with fatty liver and severe hepatic necrosis. The results suggest that alcohol consumption induced a dysregulated T-cell population that mediated hepatic necrosis following polyclonal activation with Con A.
Authors:
Q Cao; R Batey; G Pang; R Clancy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Alcoholism, clinical and experimental research     Volume:  22     ISSN:  0145-6008     ISO Abbreviation:  Alcohol. Clin. Exp. Res.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-08-28     Completed Date:  1998-08-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7707242     Medline TA:  Alcohol Clin Exp Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  723-9     Citation Subset:  IM; X    
Affiliation:
Department of Gastroenterology, John Hunter Hospital, Newcastle, NSW, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / immunology
Concanavalin A / immunology
Female
Liver Cirrhosis, Alcoholic / immunology*
Liver Cirrhosis, Experimental / immunology*
Lymphocyte Activation / immunology*
Lymphocyte Count
Rats
Rats, Wistar
T-Lymphocyte Subsets / immunology
T-Lymphocytes / immunology*
Chemical
Reg. No./Substance:
11028-71-0/Concanavalin A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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