| Project/Area Number |
12670701
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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 |
Circulatory organs internal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
NAKAGOMI Akihiro Nippon Medical School, The First Department of Int. Med., Assistant, 医学部, 助手 (60188919)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Satoshi Nippon Medical School, Assistant, 医学部, 助手 (20267123)
KUSAMA Yoshiki Nippon Medical School, Assistant Professor, 医学部, 講師 (40169983)
桜井 薫 日本医科大学, 医学部, 助手 (40256938)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | TNF-α / C-reactive protein / Heart failure / 組織因子 / 炎症性サイトカイン / C-Reactive Protein |
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| Research Abstract |
Tumor necrosis factor alpha (TNF), a proinflammatory cytokine with potent negative inotropic properties, is elaborated in patients with advanced congestive heart failure (CHF) and the levels of TNF were correlated well with New York Heart Association (NYHA) functional class (a maker of the degree of CHF).C-reactive protein (CRP), an acute phase reactant, is secreted by hepatocytes in response to interleukin 6 and CRP induces TNF on monocytes. Recently some investigators demonstrated TNF mRNA and protein in the failing human myocardium, suggesting that myocardium itself might produce TNF. On the other hand, monocytes is thought to be the major source of TNF production in response to lipopolysaccharide (LPS), so we hypotheses TNF on monocytes might be responsible for the progressive cardiac decompensation. Peripheral blood mononuclear cells (PBMC) were isolated from 10 normal subjects and 14 patients with CHF (mean EF ; 22.5 %) and were incubated with CRP, LPS and their combination and TNF levels on monocytes were determined using enzyme-linked immunosorbent assay. At the same time, plasma levels of brain natriuretic hormone (BMP ; a maker of CHF degree) were also measured. Basal (Unstimulated), CRP, LPS, and CRP+LPS induced monocyte TNF levels in CHF patients were significantly higher than those in normal subjects. In CHF patients, there was a significant correlation between BNP levels in plasma and basal and monocyte TNF levels induced by CRP+LPS, indicating that TNF on monocytes might be responsible for the progression of CHF.
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