An anti-inflammatory cytokine, Interleukin-11 : A therapeutic target against septic MODS
| Project/Area Number |
15591916
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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 |
Emergency medicine
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
KATAYAMA Hiroshi Okayama University, Hospitals, Associate Professor, 医学部・歯学部附属病院, 助教授 (90161067)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Toru Okayama University, Graduate School of Medicine and Dentistry, Instructor, 大学院・医歯学総合研究科, 助手 (40252952)
AKAGI Reiko Okayama Prefectural University, Faculty of Health and Welfare Science, Associate Professor, 保健福祉学部, 助教授 (50150967)
MORITA Kiyoshi Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (40108171)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | sepsis / liver / anti-inflammatory cytokine / interleukin-11 / endotoxin / TNF-α / iNOS / NF-κB / 抗炎症サイトカイン |
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| Research Abstract |
Excessive systemic inflammatory responses in sepsis cause severe tissue injuries leading to multiple organ failures including that of liver, the target organ as well as a source of inflammatory mediators in sepsis. Interleukin-11 (IL-11) is a pleiotropic cytokine that can suppress inflammation through the down-regulation of multiple pro-inflammatory mediators. Although it has been reported that recombinant human IL-11 (rhIL-11) may be useful in the treatment of sepsis, the effect of IL-11 on hepatic injury associated with sepsis has not been evaluated. In the present study, we examined the effect of rhIL-11 specifically on hepatic injury in a rat model of sepsis. Male Sprague-Dawley rats were injected intraperitoneally (i.p.) with bacterial lipopolysaccharide (LPS,20 mg/kg). Immediately after LPS injection, some rats were also treated with rhIL-11 (150μg/kg, i.p.). LPS treatment induced severe hepatic injury as revealed by marked increases in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities, extensive hepatocyte necrosis, tumor necrosis factor-α (TNF-α) mRNA, inducible nitric oxide synthase (iNOS) mRNA, and DNA binding activity of nuclear factor-κB (NF-κB). In contrast, rhIL-11 treatment significantly suppressed the LPS-induced hepatic injury, as judged by amelioration of all these indices. In addition, rhIL-11 treatment markedly decreased LPS-induced mortality. These results indicate that rhIL-11 possesses a potent anti-inflammatory activity that plays a protective role in the LPS-induced sepsis. Moreover, rhIL-11 may be a new drug target for sepsis.
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Report
(3 results)
Research Products
(10 results)
