Effects of long-term administration of interferon alpha in two models of liver fibrosis in rats.
OBJECTIVE
The aim of this study was to assess the effect of the early and chronic administration of interferon alpha in the prevention of hepatic fibrosis and portal hypertension.


METHODS
Rats with liver fibrosis due to bile duct ligation or CCl4 were divided into three groups: sham, placebo and interferon alpha2a 100,000 UI/day. Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and mRNA (fibronectin, procollagen alpha2(I)) contents, and serum hyaluronate. Systemic and splanchnic hemodynamics were also evaluated.


RESULTS
Interferon alpha significantly decreased fibrosis in the CCl4 model only: area of fibrosis: 13.9+/-3.7 vs 10.5+/-3.3% (p<0.05), hydroxyproline: 1.8+/-0.6 vs 1.2+/-0.2 mg/g wet liver (p<0.001), respectively placebo vs interferon alpha. There was a significant correlation between the area of fibrosis and hydroxyproline liver content (r=0.77 in the biliary model and r=0.87 in the CCl4 model, p<0.0001). Interferon decreased spleno-renal shunt blood flow (2.0+/-1.8 vs 0.9+/-0.7 ml/min; p<0.05) but not portal pressure in the CCl4 model. No significant effects were observed in rats with biliary fibrosis.


CONCLUSIONS
The early and chronic administration of interferon alpha prevents the development of liver fibrosis and porto-collateral circulation in the CCl4 model but not in the biliary model. However, the antifibrotic effects of interferon need to be confirmed in further studies.
Fort
J
J
Laboratoire d'Hémodynamique Splanchnique, Bordeaux, France.
Pilette
C
C
Veal
N
N
Oberti
F
F
Gallois
Y
Y
Douay
O
O
Rosenbaum
J
J
Calès
P
P
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001652:Bile Ducts / Q000502:physiology; D001835:Body Weight; D002252:Carbon Tetrachloride Poisoning / Q000150:complications; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006820:Hyaluronic Acid / Q000097:blood; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D006820:Hyaluronic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase