Augmentation of Anti-tumor Activity of Non-parenchymal Cells in the Liver by Continuous Administration of Recombinant Interleukin-2 : Experimental and Clinical Study

The efficacy of continuous hepatic administration of human recombinant interleukin-2 (rIL-2) was examined. In the experimental study, rIL-2 (2 x 10^5 JRU/6 days) or saline was continuously injected via the portal vein for 6 days in 18 Donryu rats (8-10 weeks, male). The rats were killed on day 0, 3, and 7 after the completion of rIL-2 or saline injection. On each day, anti-Y3 activity (natural killer (NK) activity) and anti-EL-4 activity (Iymphokine activated killer (LAK) activity) of BMCs (blood mononuclear cells) and NPCs (non-parenchymal cells) in the liver using a 4-hour <51>^Cr releasing assay. NK and LAK activities of BMCs were significantly augmented on day 0 and day 3 after rIL-2 injection. LAK activities of NPCs were also increased on day 0 and day 3. Furthermore, the NK activities of NPCs were markedly augmented on days 0, 3, and 7 after rIL-2 injection. In the clinical study, four patients with hepatocellular carcinoma (HCC) received intraarterial combined immunochemotherapy consisting of rIL-2, OK-432, adriamycin, cyclophosphamide, and famotidine before hepatic resection. The resected specimens were stained with hematoxylin-eosin and immunohistochemically using monoclonal antibodies such as CD4, CD8, CD16 and HLA-DR. Four patients with HCC who did not receive any therapy before hepatic resection were randomly selected as controls. CD8^+ and HLA-DR^+ cells were markedly infiltrated around and into the tumors in patients receiving immunochemotherapy compared with the controls. These findings suggest that pre-operative administration of rIL-2 may augment the anti-tumor activities of NPCs in the liver and reduce the liver metastases in patients with gastro-intestinal malignancy after surgery.

IL-2

門脈内持続投与

NK活性

LAK活性

肝非実質細胞

術後免疫脳