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Altered T‐Lymphocyte Responsiveness to Polyclonal Cell Activators Is Responsible for Liver Cell Necrosis in Alcohol‐fed Rats
Author(s) -
Cao Q.,
Batey R.,
Pang G.,
Clancy R.
Publication year - 1998
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1998.tb04317.x
Subject(s) - medicine , endocrinology , tumor necrosis factor alpha , concanavalin a , necrosis , cd8 , alcoholic liver disease , population , t cell , interleukin 2 , cytokine , lymphocyte , biology , chemistry , immunology , immune system , cirrhosis , biochemistry , in vitro , environmental health
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‐α 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‐α 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.