Effect of interferon gamma on intrahepatic haemodynamics of the cirrhotic rat liver.
Sublethal injury of the liver with carbon tetrachloride (CCl4) induces the modulation of hepatic stellate cells to their myofibroblast (MFB) phenotype. Pretreatment or concomitant treatment with interferon gamma (IFNgamma) has been shown to inhibit this phenomenon. The aim of this study was to investigate the influence of IFNgamma treatment (50000 IU s.c. each day for 5 days) in rats with an established cirrhosis. Cirrhosis was induced with nine doses of CCl4. Comparison of biopsies before and after treatment with IFNgamma showed that the number of MFB present, identified by their alpha-smooth muscle actin immunoreactivity, was markedly reduced. Pressure-flow curves were constructed in isolated perfused liver preparations from IFNgamma-treated and saline-treated cirrhotic rats and analysed to obtain the extrapolated zero-flow intercept (Po, an index of hepatic vascular distensibility) and the vasodilator-induced change in resistance at a flow rate of 1 mL/min per g (deltaR1, an indication of the level of intrinsic vascular tone). In IFNgamma-treated rats, portal venous pressure measured in vivo was significantly reduced compared with controls (11.9+/-1.2 vs 16.0+/-0.5 mmHg, P< 0.05), Po was lower (2.03+/-0.18 vs 2.87+/-0.32 mmHg, P<0.05) and deltaR1 was decreased (0.39+/-0.15 vs 1.02+/-0.19 mmHg/mL per min per g, P< 0.05). The findings indicate that treatment with IFNgamma is effective in reducing MFB density in established CCl4-cirrhosis in the rat and results in a marked improvement in intrahepatic haemodynamics.
Grossman
H J
HJ
Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. h.grossman@pathology.unimelb.edu.au
White
D
D
Grossman
V L
VL
Bhathal
P S
PS
D000818:Animals; D002252:Carbon Tetrachloride Poisoning; D006975:Hypertension, Portal / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D007371:Interferon-gamma / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008102:Liver Circulation / Q000502:physiology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D017082:Portal Pressure / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D007371:Interferon-gamma