Antitumor effect to IL-12 administration into the portal vein on murine liver metastasis.
OBJECTIVE
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 x 10(5) 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 micro g 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)-gamma 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.
Su
Wei
W
Department of Surgery (E1), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Kitagawa
Toru
T
Ito
Toshinori
T
Oyama
Tsukasa
T
Lee
Chun Man
CM
Kim
Yong-Kook
YK
Matsuda
Hikaru
H
D000230:Adenocarcinoma / Q000188:drug therapy*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D018664:Interleukin-12 / Q000008:administration & dosage*; D008113:Liver Neoplasms; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D018345:Mice, Knockout; D011169:Portal Vein
D000276:Adjuvants, Immunologic; D018664:Interleukin-12