Altered T-lymphocyte responsiveness to polyclonal cell activators is responsible for liver cell necrosis in alcohol-fed rats

被引:20
作者
Cao, Q
Batey, R
Pang, G
Clancy, R
机构
[1] John Hunter Hosp, Dept Gastroenterol, Newcastle, NSW 2310, Australia
[2] Univ Newcastle, Discipline Pathol, Newcastle, NSW 2308, Australia
关键词
alcoholic liver disease; Con A; IL-6; TNF-alpha; CD4(+) T cells;
D O I
10.1097/00000374-199805000-00026
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
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.
引用
收藏
页码:723 / 729
页数:7
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