| Project/Area Number |
61480268
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Okayama University |
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Principal Investigator |
ORITA Kunzo Okayama University Medical School, First Department of Surgery Professor, 医学部, 教授 (20033053)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIKAWA Yasuaki Okayama University Medical School, First Department of Surgery Instructor, 医学部附属病院, 助手 (00152851)
TANAKA Noriaki Okayama University Medical School, First Department of Surgery Assistant Profess, 医学部附属病院, 講師 (10127566)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | hepatic regeneration / NK cell / LAK cell / interleukin 2 / cyclosporine A / FK506 / neuraminidase / liver cirrhosis / 肝部分切除 / 活性化キラー細胞 / ILー2 / 抗腫瘍活性 / 部分肝切除 / 肝癌 / 特異的キラーTリンパ球 / 非特異的キラーリンパ球 |
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| Research Abstract |
It has been reported that regulatory factors of regeneration are present in the liver. Another mechanism controlling liver regeneration was posturated from the following observations that partial hepatectomy stimulates the proliferation of lymphocytes, and augments the function of the NK/LAK sells which exhibited cytotoxicity against regenerating liver cells.
The effects of passive transfer of LAK cells on liver regeneration were examined by ^3H-thymidine uptake and bromodeoxyuridine (BrdU) labeling methods after resection of 70% volume of the liver. LAK cells were infused 12h after hepatectomy and the effects on regeneration of liver cells were examined 36h later.
The transfusion of LAK cells induced significant inhibition of liver regeneration at a dose of 5-10*10^7cells.Neuraminidase treatment of LAK cells enhanced the suppressive effect furthermore.
The intraperitoneal injection of IL-2 after partial hepatectomy stimulated NK/LAK cells, and inhibited the regeneration of liver. Since IL-2 production of spleen cells was augmented after hepatectomy, lymphocytes such as NK/LAK cells in the liver may regulate liver regeneration by IL-2 stimulation. Therefore, it was expected that IL-2 inhibitors such as cyclosporine and FK506 after hepatectomy enhance the regeneration of the remnant liver.
By administration of CsA of 5-10mg/kg pre- and post- operation, the BrdU labeling index of the liver significantly increased in the range of 159-226%. The same effects were also observed by the administration of FK506.
Based on these results, CsA andFK506 would appear to stimulate liver cell proliferation by inhibiting IL-2 production and suppressing NK/LAK cell activity.
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