PMID- 12062635
OWN - NLM
STAT- MEDLINE
DCOM- 20021120
LR  - 20190916
IS  - 0741-8329 (Print)
IS  - 0741-8329 (Linking)
VI  - 27
IP  - 1
DP  - 2002 May
TI  - Lymphocyte-mediated liver injury in alcohol-related hepatitis.
PG  - 37-41
AB  - The pathogenesis of alcohol-related liver disease (ALD) remains inadequately 
      explained. Increasing alcohol intake is associated with an increased risk of ALD, 
      but many heavy drinkers develop no liver damage. An explanation for ALD 
      susceptibility requires theories that extend beyond a biochemical understanding 
      of alcohol metabolism. Several hepatic cell populations are involved in the 
      pathogenesis of liver injury. The liver-associated lymphocyte (LAL) response to 
      alcohol intake plus immune stimulation may determine susceptibility to liver 
      damage. We have isolated rat LALs and demonstrated the following: (1) 
      Liver-associated lymphocytes differ from the peripheral blood lymphocyte pool; 
      the CD8:CD4 ratio is higher in the LAL population than in peripheral blood. (2) 
      Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 production by these 
      cells is suppressed by regular alcohol intake. (3) Tumor necrosis factor-alpha 
      and interleukin-6 production by LALs is increased after parenteral administration 
      of concanavalin A (Con A) and by Con A in in vitro LAL cultures obtained from 
      healthy (control) and ethanol-consuming rats. (4) In vivo stimuli that lead to 
      increased cytokine production by LALs lead, within 12-24 h, to increased 
      hepatocyte necrosis [elevated alanine aminotransferase (ALT) levels] and 
      apoptosis. (5) Liver-associated lymphocytes isolated from ethanol-consuming rats, 
      transferred to non-ethanol-consuming rats, confer on the latter animals an 
      ethanol-consuming response to Con A. (6) Cytokine release by LALs is 
      quantitatively as significant as that from Kupffer cells after exposure to 
      lipopolysaccharide. (7) In co-culture studies inhibition of TNF-alpha activity 
      reduces hepatocyte apoptosis induced in the presence of activated LALs. (8) 
      Finally, nuclear factor-kappa B inhibition decreases production of nitric oxide 
      and TNF-alpha, with an associated reduction in hepatocyte apoptosis. In summary, 
      our study findings support the suggestion that a role for LALs exists in the 
      pathogenesis of alcohol and Con A-mediated liver disease.
FAU - Batey, Robert G
AU  - Batey RG
AD  - Department of Gastroenterology, John Hunter Hospital, New Lambton Heights, 
      Newcastle 2305, NSW, Australia. rbatey@hunter.health.nsw.gov.au
FAU - Cao, Qi
AU  - Cao Q
FAU - Gould, Belinda
AU  - Gould B
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Alcohol
JT  - Alcohol (Fayetteville, N.Y.)
JID - 8502311
SB  - IM
MH  - Animals
MH  - Hepatitis, Alcoholic/immunology/pathology
MH  - Humans
MH  - Liver/immunology/*pathology
MH  - Lymphocytes/immunology/*pathology
RF  - 36
EDAT- 2002/06/14 10:00
MHDA- 2002/11/26 04:00
CRDT- 2002/06/14 10:00
PHST- 2002/06/14 10:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/06/14 10:00 [entrez]
AID - S0741832902002136 [pii]
AID - 10.1016/s0741-8329(02)00213-6 [doi]
PST - ppublish
SO  - Alcohol. 2002 May;27(1):37-41. doi: 10.1016/s0741-8329(02)00213-6.