Protective effect of an apoptosis inhibitor in a new model of hepatitis induced by interleukin-4 in the rat
Chetritt, J.; David, A.; Guillot, C.; Tesson, L.; Laboisse, C.; Soulillou, J.P.; Anegon, I.
Gastroenterologie Clinique et Biologique 23(10): 1021-1027
1999
ISSN/ISBN: 0399-8320 PMID: 10592873 Document Number: 511008
Interleukin-4 is a cytokine with pleiotropic effects on many cells. The effects of its expression on the liver remain unclear. To obtain organ-localized cytokine expression and analyze its effect on the liver, recombinant adenovirus with coding sequences of interleukin-4 were transduced to rat livers. Adenovirus with coding sequences of rat interleukin-4 were injected into the portal vein of Wistar rats. Microscopic examination of the liver was performed. The effects of interleukin-4 were confirmed in vitro on primary cultured rat hepatocytes. The same analysis was performed after intraperitoneal injection of l'YVADcmk, an inhibitor of the interleukin 1 converting enzyme. Interleukin-4 expression due to the recombinant adenovirus produced dose-related, potentially lethal, severe hepatitis. This hepatitis was characterized by a leucocyte infiltrate mainly composed of eosinophilic polymorphonuclear and mast cells with numerous apoptotic hepatocytes. Intraperitoneal injection of YVADcmk decreased hepatocyte apoptosis and biological hepatitis and prevented death. These results suggested that YVADcmk might be used in fulminant hepatitis in which apoptosis is predominant.