2000 Fiscal Year Final Research Report Summary
Prophylactic therapies to treat septic shock - Study using vascular permeability in the skin of mice
| Project/Area Number |
11672279
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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 |
応用薬理学・医療系薬学
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
FUJII Emiko Tokyo Women's Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (20075493)
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| Co-Investigator(Kenkyū-buntansha) |
IRIE Kaoru Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (50075496)
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| Project Period (FY) |
1999 – 2000
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| Keywords | endotoxin / lipoteichoic acid / vascular permeability / prostaglandin / nitric oxide / septic shock / endotoxin tolerance / glucocorticoid |
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| Research Abstract |
The potency of lipoteichoic acid (LTA) to induce microvascular inflammatory response has not been clarified. We have shown that s.c. injection of endotoxin (LPS) increases local plasma leakage in the skin of mice (Fujii et al., 1996). In this study, we compared the effect of LTA and LPS on local plasma leakage in the mouse skin. Because our previous study had shown that pretreatment with low-dose LPS induces tolerance (Fujii et al., 1996), we also examined whether pretreatment with low-dose LTA induces tolerance as does LPS.Subcutaneous injection of LTA in mice that were preinjected i.v. with Pontamine sky blue dye increased local dye leakage in the skin. The LTA-induced dye leakage was inhibites by indomethacin, diphenhydramine, and PAF antagonist but not by inhibitors of nitric-oxide (NO) synthase, cycloxygenase-2, or guanylate cyclase or by antibodies against tumor necrosis factor-α (TNF-α) or interleukin-1α (IL-1α). Among the inflammatory mediators, eicosanoids, PAF, and histamine mediate the effect of both LTA and LPS, whereas NO, TNF-α, and IL-1α may not play a major role in LTA-induced dye leakage. The dye leakage induced by LTA was not affected in LTA-primed mice. Serum corticosterone levels, which were suggested to induce tolerance, were not increased by LTA pretreatment but were increased by LPS.These results suggest that endogenous glucocorticoids may play a role for development of LPS-induced tolerance in microcirculation. The tolerance induced by LPS may provide a potential basis for the treatment of sepsis, although LTA may not be useful as a prophylactic therapy of septic shock.
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