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Journal of Hepato-Biliary-Pancreatic Surgery

, Volume 9, Issue 4, pp 503–510 | Cite as

Antitumor effect to IL-12 administration into the portal vein on murine liver metastasis

  • Wei Su
  • Toru Kitagawa
  • Toshinori Ito
  • Tsukasa Oyama
  • Chun Man Lee
  • Yong-Kook Kim
  • Hikaru Matsuda

Abstract.

Background/Purpose: Interleukin (IL)-12 has been shown to possess potent antitumor activity, and an antitumor effect of systemic IL-12 administration has been reported in liver metastasis models.

Methods: In this study, we examined the usefulness of local IL-12 administration into the portal system in the treatment of liver metastasis. First, we confirmed the antitumor effect of recombinant IL-12 (rIL-12) on MC-38 tumors in an intracutaneous model. In the murine liver metastasis model, 1 × 105 of MC-38 cells were injected into the portal vein on day 0, and the spleen was transpositioned subcutaneously for administration of rIL-12 continually into the portal system. From days 3 to 7, 0.1 μg rIL-12 was administered intraperitoneally or intrasplenicly, while Hanks' Balanced Salf Solution (HBSS) was injected intrasplenicly in the control group.

Results: The liver weight in the rIL-12 intraperitoneal treatment group (1.88 ± 0.37 g) and that in the rIL-12 intrasplenic treatment group (1.43 ± 0.21 g) were significantly less than that in the HBSS group (2.86 ± 0.74 g; P < 0.05). The numbers of metastatic nodules in the rIL-12 intraperitoneal treatment group (22.3 ± 17.1) and in the rIL-12 intrasplenic treatment group (12.4 ± 13.8) were significantly less than that in the HBSS group (137.1 ± 44.9; P < 0.05). Complete regression of the tumor was observed in one of six mice in the rIL-12 intrasplenic treatment group. This antitumor effect of rIL-12 on MC-38 liver metastasis was not observed in interferon (IFN)-γ knockout mice. Intraportal administration of IL-12-transduced fibroblasts, which were syngeneic to C57BL/6 mice, had an antitumor effect in the MC-38 liver metastasis model.

Conclusions: These results suggested that the local administration of IL-12 into the portal system would be a useful strategy for the treatment of liver metastasis.

Key words IL-12   Liver metastasis   Fibroblast 

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Copyright information

© Springer-Verlag Tokyo 2002

Authors and Affiliations

  • Wei Su
    • 1
  • Toru Kitagawa
    • 1
  • Toshinori Ito
    • 1
  • Tsukasa Oyama
    • 1
  • Chun Man Lee
    • 1
  • Yong-Kook Kim
    • 1
  • Hikaru Matsuda
    • 1
  1. 1.Department of Surgery (E1), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanJP

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