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2000 Fiscal Year Final Research Report Summary

Regulation of pro- and anti-inflammatory cytokine responses by Kupffer cell in endotoxin-enhanced reperfusion injury after total hepatic ischemia

Research Project

Project/Area Number 10671169
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

SUZUKI Shohachi  Hamamatsu University School of Medicine, Department of Surgery II, Assistant Professor, 医学部・附属病院, 講師 (20196827)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Satoshi  Hamamatsu University School of Medicine, Department of Surgery II, Professor, 医学部, 教授 (00090027)
Project Period (FY) 1998 – 2000
KeywordsHepatic ischemia / Reperfusion injury / Kupffer cell / TNF-α / MIP-2 / Gadolinium chloride / Endotoxin / IL-10
Research Abstract

Background. This study was designed to investigate the implication of Kupffer cell for pro- and anti-inflammatory cytokine responses in endotoxin-enhanced reperfusion injury after total hepatic ischemia.
Methods. Male rats pretreated with either normal saline solution (NS group) or gadolinium chloride (7 mg/kg) for 2 days to inhibit Kupffer cell function (GC group) were subjected to 60 minutes of total hepatic ischemia. These animals given either normal saline solution or sublethal endotoxin (1 mg/kg) via the portal vein at reperfusion were subdivided into NS-N, NS-E, GC-N and GC-E groups. In addition to 7-day survival rates, plasma aspartate aminotransferase (AST), tumor necrosis factor alpha (INF-α), macrophage inflammatory protein-2 (MIP-2), and interleukin-10 (IL-10) levels and hepatic neutrophil infiltration were determined 1, 3, and 6 hours after reperfusion.
Results. All animals without endotoxin administration at reperfusion tolerated 60 minutes of hepatic ischemia. While 7-day survival rate of NS-E group was reduced to 30%, that of GC-E group significantly improved to 80%. Cytokine responses in NS-E group were composed of the maximum TNF-α and IL-10 levels 1 hour after reperfusion with a subsequent peak of MIP-2 levels. The highest AST levels and extensive hepatic necrosis with more neutrophil infiltration were observed 6 hours after reperfusion. Pretreatment with GdCl3 significantly suppressed TNF-α production and increased IL-10 production 1 hours of reperfusion when compared to those in NS-E group, which led to decline in MIP-2 production and amelioration of functional and structural liver damage.
Conclusions. Kupffer cells were implicated in endotoxin-enhanced reperfusion injury after hepatic ischemia with increased MIP-2 production mediated by TNF-α and IL-10. Blockade of Kupffer cells may have a great potential to attenuate the insult via modulation of these cytokine responses.

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Shohachi Suzuki: "The roles of platelet-activating factor and endothelin-1 in renal damage after total hepatic ischemia and reperfusion"Transplantation. 69. 2267-2273 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木昌八: "肝虚血・再灌流障害とサイトカイン"日外会誌. 100. 325-330 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shohachi Suzuki: "Role of cytokines in hepatic ischemia and reperfusion injury"J Jpn Surg Soc. 100-5. 325-330 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shohachi Suzuki: "The roles of platelet-activating factor and endothelin-1 in renal damage after total hepatic ischemia and reperfusion."Transplantation. 69-11. 2267-2273 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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