2004 Fiscal Year Final Research Report Summary
Analysis of altered immunological responses under abnormal environmental conditions, including environmental temperature, and the trial of its active modulation for the treatment of critically ill patients
| Project/Area Number |
14370364
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Keio University |
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Principal Investigator |
AIKAWA Naoki Keio University, Department of Medicine, Professor, 医学部, 教授 (40110879)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Katsunori Hamamatsu University, School of Medicine, Department of Medicine, Professor, 医学部, 教授 (20124927)
HORI Shingo Keio University, Department of Medicine, Associate professor, 医学部, 助教授 (80129650)
FUJISHIMA Seitaro Keio University, Department of Medicine, Assistant professor, 医学部, 講師 (00173419)
SEKINE Kazuhiko Keio University, Department of Medicine, Instructor, 医学部, 助手 (90296715)
YOH Kikuo Keio University, Department of Medicine, Instructor, 医学部, 助手 (00327644)
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| Project Period (FY) |
2002 – 2004
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| Keywords | hyperoxia / hyperthermia / hypothermia / cytokine / HGF / coagulation and fibrinolysis / ARDS / sepsis |
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| Research Abstract |
1)Effect of environmental and oxygen tension changes on cellular functions : We incubated human whole blood with lipopolysaccharide (LPS) at various temperatures and found that both hypoxia and hyperoxia inhibited the production of interleukin-8 (IL-8).
We next exposed human umbilical vein endothelial cells (HUVEC) to different oxygen tensions and examined the changes in cellular functions. The expression of IL-8 mRNA after LPS stimulation was accelerated under hyperoxia, which was preceded by the significant increase in phospho-JNK. Furthermore, when HUVECs were continually monitored with CCD cameras under various conditions, these cells moved around in the same manner, irrespective of the presence of LPS, TNF, or hyperoxia. However, only when HUVECs were cultured under the co-presence of TNF and hyperoxia, most cells finally died.
2)Pathophysiology of patients under hyperthermia and burn injuries : In patients suffered from altered level of consciousness after bathing with high tempera
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ture, serum levels of IL-6, IL-8, IL-10 were abnormally high and in patients with major burn injuries the plasma levels of IL-18 was lower in patients. We next analyzed plasma cytokines and HGF in 50 SIRS patients and found their increase as well as relative independence of HGF from other cytokines. Finally, we analyzed coagulation/fibrinolysis and neutrophil elastase-related factors in 64 SIRS patients and found a significant correlation between D dimer and TAT, PIC, e-XDP. In ARDS patients, serum levels of fibrinogen, D dimer elastase/alpha 1-AT complex, e-XDP were increased.
3)Altered immunological status after burn injury and its pharmacological normalization in mice : We developed a mouse model of 30% third degree skin burn and found a significant decrease in hepatic IL-18 contents after burn injury. In these mice, survival after a sublethal dose of LPS challenge were significantly lowered and IL-18 supplementation significantly ameliorated the survival as well as augmented MIP-2 production by splenic cells after LPS challenge. Less
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