This research was supported by The Bushell Foundation, Australia.
Altered T-Lymphocyte Responsiveness to Polyclonal Cell Activators Is Responsible for Liver Cell Necrosis in Alcohol-fed Rats
Article first published online: 30 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 22, Issue 3, pages 723–729, May 1998
How to Cite
Cao, Q., Batey, R., Pang, G. and Clancy, R. (1998), Altered T-Lymphocyte Responsiveness to Polyclonal Cell Activators Is Responsible for Liver Cell Necrosis in Alcohol-fed Rats. Alcoholism: Clinical and Experimental Research, 22: 723–729. doi: 10.1111/j.1530-0277.1998.tb04317.x
- Issue published online: 30 MAY 2006
- Article first published online: 30 MAY 2006
- Received for publication April 21, 1997; accepted December 23, 1997
- Key Words: Alcoholic Liver Disease;
- Con A;
- CD4+ T cells
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.