2006 Fiscal Year Final Research Report Summary
Early detection of postoperative sepsis and organ dysfunction using cDNA micro-array and therapeutic strategy for these complications by anti-TLR antibody.
| Project/Area Number |
17591374
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Chiba University |
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Principal Investigator |
KIMURA Fumio Chiba University, Graduate School of Medicine, Assistant professor, 大学院医学研究院, 助教授 (70334208)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Masaru Chiba University, Graduate School of Medicine, Professor, 大学院医学研究院, 教授 (70166156)
YOSHIDOME Hiroyuki Chiba University, Graduate School of Medicine, Associate Professor, 大学院医学研究院, 講師 (10312935)
OHTSUKA Masayuki Chiba University, Graduate School of Medicine, Assistant Professor, 大学院医学研究院, 助手 (90334185)
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| Project Period (FY) |
2005 – 2006
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| Keywords | organ dysfunction / postoperative sepsis / cDNA micro-array / anti-TLR antibody / GATA3 / T-bet / sC30 |
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| Research Abstract |
Background/Objectives : Aggressive hepatobiliary pancreatic surgery has been associated with high complication rates. Early detection of postoperative sepsis and organ dysfunction using cDNA micro-array and transcription-polymerase chain reaction (RT-PCR) was evaluated in patients undergoing hepatobiliary pancreatic surgery. Furthermore, therapeutic effects of anti-TLR2, 4 antibodies on these complications were determined in animal models with peritoneal sepsis or obstructive jaundice.
Methods : Plasma concentrations of interleukin (IL)-6, IL-10, soluble lymphocyte activation gene (sLAG) -3, and soluble CD30 (sCD30) were determined by ELISA perioperatively in consecutive 56 patients who underwent hepatobiliary pancreatic surgery. Gene expression in PBMCs was analysed by cDNA micro-array, and expression levels of T-bet, GATA-3, TLR2, and TLR4 mRNA in PBMCs were confirmed by reverse RT-PCR.
Effects of anti-TLR2, 4 antibodies on sepsis were determined in animal models with peritoneal sepsis
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or obstructive jaundice.
Results : Of the 56 patients, 30 patients had postoperative infection. Postoperative plasma levels of IL-6 and IL-10 were significantly higher in patients with postoperative infection than in those without infection (p<0.05). sCD30 levels were significantly higher preoperatively, and remained higher by postoperative day 7 in patients with postoperative infection (p<0.05). sLAG-3 levels were not significantly different between two groups. GATA-3 mRNA expression level was significantly higher preoperatively, and remained higher by postoperative day 7 in patients with postoperative infection (p<0.05). T-bet mRNA expression level was significantly higher on postoperative days 3, 7, and 14 in patients with postoperative infection (p<0.05). TLR2 and TLR4 mRNA expression levels were significantly higher on postoperative day 3 in patients with postoperative infection (p< 0.05). Preoperative expression levels of GATA-3 mRNA correlated significantly with those of TLR2 and TLR4 mRNA (p<0.05). Anti-TLR2, 4 antibodies were not effective in animal models with peritoneal sepsis or obstructive jaundice.
Conclusions : These results suggest that preoperative Th1/Th2 balance shifts toward Th2 dominance in patients with postoperative infection, and preoperative expression levels of circulating sCD30 and GATA3 mRNA in PBMCs are the novel markers predicting postoperative sepsis and organ dysfunction. Less
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