INFLUENCE OF CONTINUOUS INTERLEUKIN-2 ADMINISTRATION VIA THE PORTAL-VEIN ON LIVER-REGENERATION FOLLOWING PARTIAL-HEPATECTOMY IN RATS

We have reported the efficacy of intraarterial-combined immunochemothe rapy including interleukin-2 (IL-2) for unresectable hepatocellular ca rcinoma (HCC). To further test this therapy for prevention of intrahep atic recurrence after hepatectomy, the influence of lL-2 on liver rege neration was examined using mitotic index (MI) and the bromodeoxyuridi ne (BrdU) labeling index (LI) in 70% hepatectomized Donryu rats. In ad dition, gap junction appearance, which may change during liver regener ation, was analyzed using a monoclonal antibody (HAM8). Serum albumin, alanine transaminase, and total bilirubin (TB) levels were also evalu ated. IL-2 (45,000 Japanese reference units [JRU]/d) or saline was adm inistered continuously via the portal vein immediately after hepatecto my using an infusion pump. We also examined the influence of IL-2 on L iver regeneration after hepatectomy with splenectomy. No difference in the weight of the liver, serum albumin, alanine transaminase, or TB w as observed in any groups at 1, 2, or 4 days after hepatectomy. Neithe r IL-2 nor splenectomy influenced MI and BrdU LI at all three points. Gap junctions began to disappear after hepatectomy and reached a minim um on day 2 in all groups. Four days after hepatectomy, the density of the reappearing gap junctions was markedly lower in groups treated wi th IL-2 than in those receiving saline with or without splenectomy. Ho wever, the density returned to close to preoperative levels 6 days aft er hepatectomy in all groups. Continuous portal infusion of IL-2 trans iently disturbed gap junction reappearance during liver regeneration. However, no other parameters of Liver regeneration or liver functions differed. These results suggest that the Liver regeneration after part ial hepatectomy may be suppressed by the administration of IL-2, even though the suppression may not be harmful for overall recovery of the resected liver. However, it seems that hepatic IL-2 administration can be performed without serious complications after hepatectomy.