Effect of interferon-alpha(2b) administration on rat liver regeneration after partial hepatectomy

The purpose of the present study was to delineate the effect of interferon-alpha(2b) (IFN-alpha(2b)) administration on the liver regenerative capacity after partial hepatectomy in rats. The administration of IFN-alpha(2b) simultaneously with partial hepatectomy did not affect hepatic proliferation in a statistically significant manner. When IFN-alpha(2b) was administered either 2 or 12 hr postoperatively, an inhibition of hepatocyte proliferation was observed 24 hr postoperatively, while at further time intervals up to 48 hr, DNA synthesis remained similar to that observed in the simply partially hepatectomized rats, The enzyme thymidine kinase (TK), has been implicated in the suppression of proliferation in interferon-treated cell cultures, In all IFN-alpha(2b)-treated groups of rats, alterations of TK activity were observed without being correlated to the liver regenerative status, Additionally, the administration of the polyamine putrescine in partially hepatectomized rats treated at the time of surgery with IFN strongly enhanced TK activity, but did not affect DNA biosynthesis, In the above-mentioned in vivo model of controlled cellular proliferation, the administration of IFN-alpha(2b) affected the rate of hepatocyte proliferation depending on the time of its administration; this effect was not correlated to the enzymatic activity of TK, as inhibited TK activity is responsible for the suppressed DNA synthesis in in vitro systems.