[Protective effect of an apoptosis inhibitor in a new model of hepatitis induced by interleukin-4 in the rat].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These results suggested that YVADcmk might be used in fulminant hepatitis in which apoptosis is predominant.
Chetritt
J
J
Unité INSERM U-437, Institut de Transplantation et de Recherche en Transplantation, Nantes.
David
A
A
Guillot
C
C
Tesson
L
L
Laboisse
C
C
Soulillou
J P
JP
Anegon
I
I
D000208:Acute Disease; D000256:Adenoviridae / Q000235:genetics*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D005822:Genetic Vectors; D006505:Hepatitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D011995:Recombination, Genetic; D013997:Time Factors; D014158:Transcription, Genetic; D014161:Transduction, Genetic
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015847:Interleukin-4
Effet protecteur d'un peptide inhibiteur de l'apoptose dans un nouveau modèle d'hépatite induite par l'interleukine-4 chez le rat.