| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥11,200,000 (Direct Cost: ¥11,200,000)
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| Research Abstract |
We investigated the significance of polymorphonuclear neutrophil cell death in surgical stress. Obtained results are as follows :
(1) Exudative PMN apoptosis was markedly inhibited on postoperative day 1 and then increased in a time-dependent manner. IL-6 and GM-CSF were related to inhibit exudative PMN apoptosis, while TNF-a and IL-10 were related to increase apoptosis. ROI production and CD16 expression of exudative PMNs were augmented when PMN apoptosis was inhibited in the early postoperative period. Understanding the mechanisms of PMN apoptosis and its pathophysiological significance at local inflammatory sites in vivo may help in the design of more rational treatments.
(2) In vitro IL-6 and GM-CSF inhibited apoptosis of PMN isolated from healthy volunteers. Moreover, IL-10 reduced the inhibitory effect of IL-6 on PMN apoptosis.
(3) Low doses of live E. coli inhibits predominantly PMN apoptosis, whereas a high dose of E. coli increases necrosis. Augmented PMN bactericidal function, via inhibition of PMN cell death, may be beneficial for host defense against bacterial infection and/or sepsis.
(4) Antibiotics such as ABPC, CEZ, CPZ and LMOX kill bacteria by a mode of filament formation, leading to excessive endotoxin release, cytokine production and necrosis of PMNs. In contrast, IMP, killing bacteria by a mode of spheroplast, inhibit excessive endotoxin release, PMN cytokine production, and necrosis, and induced PMN apoptosis. Antibiotic choices may be based on their PMN necrosis inducing property as well as their sensitivity spectrum for the clinical improvement of therapy of severe infection and/or sepsis.
(5) GH pretreatment downregulates Fas expression on PMNs, inhibits apoptosis and upregulates ROI producdon of PMNs. GH pretreatment also increases monocyte ROI production. Although activated PMNs have potentially harmful aspects, our results suggest that GH may improve host defense mainly through enhancement of the PMN functional life span.
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