Hepatic apoptosis and proliferation in male and female rats fed alcohol: role of cytokines.
BACKGROUND
The female liver is more sensitive to the toxic effect of chronic alcohol intake than the male liver. The aim of the study was to compare the influence of gender and sex hormonal status on apoptosis and cell proliferation following chronic ethanol intake.


METHODS
Male and female rats were pair fed for 8 weeks a liquid diet containing 36% of their total daily calories as ethanol (ETOH group) or sucrose (control group). Liver samples were analyzed for apoptosis and hepatocyte proliferation by immunohistochemistry. The hepatic production of factors able to influence cell death and proliferation, such as tumor necrosis factor alpha (TNFalpha) and interleukin 6 (IL-6) were determined.


RESULTS
In both male and female rats, ethanol intake promoted apoptosis in the liver. This effect of ethanol was more evident in female than male rat livers. Hepatic TNFalpha levels, which promote apoptosis, are significantly more elevated in female than in male livers. Hepatic IL-6 production, which promotes hepatocyte proliferation, was induced by ethanol only in males, but not female animals.


CONCLUSIONS
This observed difference in cytokine responses may contribute to the enhanced sensitivity of female liver to EtOH-induced injury.
Colantoni
Alessandra
A
Loyola University Chicago, Maywood, Illinois, USA.
Idilman
Ramazan
R
De Maria
Nicola
N
La Paglia
Nancy
N
Belmonte
Joseph
J
Wezeman
Frederick
F
Emanuele
Nicholas
N
Van Thiel
David H
DH
Kovacs
Elizabeth J
EJ
Emanuele
Mary Ann
MA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol