Influence of Continuous Interleukin-2 Administration via the Portal Vein on Liver Regeneration after Partial Hepatectomy in Rats

We have reported the efficacy of intra-arterial-combined immunochemotherapy including interleukin2 (IL-2) for unresectable hepatocellular carcinoma (HCC). To further test this therapy for prevention of intrahepatic recurrence after hepatectomy, the influence of IL-2 on liver regeneration was examined using the bromodeoxyuridine (BrdU) labeling index (LI) in 70% hepatectomized Donryu rats. In addition, gap junction appearance was analyzed using a monoclonal antibody (HAM 8). IL-2 (45,000 JRU/day) or saline was administered continuously via the portal vein immediately after hepatectomy. We also examined the influence of IL-2 on liver regeneration after hepatectomy with splenectomy. No difference in the weight of the liver, Serum albumin, GPT, or total bilirubin was observed in any groups at 1, 2, or 4 days after hepatectomy. Neither IL-2 nor splenectomy influenced BrdU LI at all three points. Gap junctions began to disappear after hepatectomy and reached a minimum on day 2 in all groups. Four days after hepatectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than in those receiving saline with or without splenectomy. However, the density at 6 days after hepatectomy in all groups was identical to the density in normal liver. Continuous portal infusion of IL-2 transiently disturbed gap junction reappearance during liver regeneration. However, no other parameters of liver regeneration or liver functions differed. These results suggest that intrahepatic IL-2 administration can be performed without serious complications after hepatectomy.

70%肝切除後肝再生

Interleukin-2 持続肝血管内投与

Gap junction

BrdU