Effect of interferon gamma on intrahepatic haemodynamics of the cirrhotic rat liver

Sublethal injury of the liver with carbon tetrachloride (CCI₄) induces the modulation of hepatic stellate cells to their myofibroblast (MFB) phenotype. Pretreatment or concomitant treatment with interferon gamma (IFNγ) has been shown to inhibit this phenomenon. The aim of this study was to investigate the influence of IFNγ treatment (50 000 IU s.c. each day for 5 days) in rats with an established cirrhosis. Cirrhosis was induced with nine doses of CCI⁴. Comparison of biopsies before and after treatment with IFNγ showed that the number of MFB present, identified by their α-smooth muscle actin immunoreactivity, was markedly reduced. Pressure-flow curves were constructed in isolated perfused liver preparations from IFNγ-treated and saline-treated cirrhotic rats and analysed to obtain the extrapolated zero-flow intercept (P⁰, an index of hepatic vascular distensibility) and the vasodilator-induced change in resistance at a flow rate of 1 mL/min per g (ΔR₁ an indication of the level of intrinsic vascular tone). In IFNγ-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), P₀ was lower (2.03 ± 0.18 vs 2.87 ± 0.32 mmHg, P < 0.05) and ΔR₁ 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 IFNγ is effective in reducing MFB density in established CCI₄-cirrhosis in the rat and results in a marked improvement in intrahepatic haemodynamics.