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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-8-28
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0145-6008
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
723-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Altered T-lymphocyte responsiveness to polyclonal cell activators is responsible for liver cell necrosis in alcohol-fed rats.
pubmed:affiliation
Department of Gastroenterology, John Hunter Hospital, Newcastle, NSW, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't