<Originals>Intra-hepatic immunopharmacological effects of Interleukin-2,Mitomycin C and 5-Fluorouracil infusion via portal vein in dog
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概要
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A pilot study of interleukin-2 (IL-2) plus mitomycin C (MMC) and 5-fluorouracil (5-FU) (IL-2・MF) infusion through the hepatic artery in patients with liver metastasis from colorectal cancer has given favorable therapeutic results. To clarify the mechanism underlying this effect, selective portal perfusion of IL-2・MF was done in dogs and the immunological responses including natural killer (NK) and lymphokineactivated killer (LAK) activity and histological changes in the liver were assessed with appropriate controls. Mononuclear cells isolated from the liver by sinusoidal lavage showed marked cytotoxic activity against NK-resistant, canine sarcoma cells in a ^<51>Cr. release assay. In contrast, control groups including chemoinfusion (MF), or saline infusion, did not show any significant change in the liver. Mononuclear cells obtained from the liver following MF, or saline perfusion did not show any significant cytolytic activity against NK-resistant target cells in this assay. Electron microscopic analysis of the liver following IL-2・MF infusion showed a significant accumulation of lymphocytes and large granular lymphocytes (LGL ; pit cells) in the sinusoidal lumens. The pharmacokinetics study revealed less than 10% reduction in the 5-FU level in the liver tissue in dogs given IL-2・MF 1 hour after infusion. By contrast, 5-FU level in the MF group was significantly decreased within 15 minutes after infusion at the same doses. These findings suggest that the anti-tumor effects of IL-2・MF infusion consist of at least two main pathways, namely the dramatic accumulation of cytotoxic cells in the liver by IL-2 (imnunological pathway) and the increase of hepatic extraction of chemotherapeutic agents due to the elevation of permeability of hepatic sinusoidal endothelium by IL-2 (pharmacological pathway).
- 近畿大学の論文
著者
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OKUNO Kiyotaka
First Department of Surgery, Kinki University School of Medicine
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HIROHATA Takeshi
First Department of Surgery, Kinki University School of Medicine
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Hirohata Takeshi
First Department Of Surgery Kinki University School Of Medicine
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Okuno Kiyotaka
First Department Of Surgery Kinki University School Of Medicine
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Hirohata Takeshi
Division Of Cardiology Department Of Internal Midicine Kinki University School Of Medicine
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