| Project/Area Number |
03557021
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
細菌学
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| Research Institution | Hokkaido University |
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Principal Investigator |
NAKANE Akio Hokkaido University School of Medicine Assistant Professor, 医学部, 助教授 (30164239)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Yu-ichiro Torey Industries, Inc.Basci Research Institute Chief Investigator, 基礎研究所, 主任研究員
KOHANAWA Masashi Hokkaido University School of Medicine Instructor, 医学部, 助手 (90234806)
ASANO Misako Hokkaido University School of Medicine Instructor, 医学部, 助手 (90202598)
MINAGAWA Tomonori Hokkaido University School of Medicine Professor, 医学部, 教授 (40001903)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 1993: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥6,500,000 (Direct Cost: ¥6,500,000)
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| Keywords | MRSA / Listeria monocytogenes / Staphylococcus aureus / Cytokine / IFN-gamma / TNF / IL-6 / Bacterial infectious diseases / LPS / 致死感染 / 予防 / 治療 / 抗ヒトTNFmAb / 抗マウスTNFmAb / 抗マウスIFN-γmAb / 抗CD3mAb / デキサメタゾン / Tリンパ球サブセット |
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| Research Abstract |
We investigated development of the prophylaxis and therapy of severe bacterial infectious diseases by blockade of the cytokine cascade which is induced by the lethal infections with Listeria monocytogenes and Staphylococcus aureus (MRSA) in the mouse models.
1. The high titers of endogenous gamma interferon (IFN-gamma), tumor necrosis factor (TNF) and interleukin-6 (IL-6) were detected in the bloodstreams and organs of the infected mice just before death.
2. The administration of monoclonal antibodies (mAbs) to IFN-gamma, TNF or IL-6 into L.monocytogenes-infected mice did not affect the lethal infection, whereas anti-IFN-gamma mAb protected MRSA-infected mice from the lethal infection. The protective effect was observed when the mAb was administered either before or after infection. The Protective effect of anti-IFN-gamma mAb was also showed in mice which were suffered from Escherichia coli-derived lipopolysaccharide-induced shock.
3. The protective effect was demonstrated in mice which received a lethal infection with L.monocytogenes when the cytokine cascade was suppressed by the treatment of glucocorticoid, dexamethasone.
4. The protective effect was demonstrated in mice which received a lethal infection with L.monocytogenes when the cytokine cascade was induced by stimulation of T lymphocytes with the mAb to CD3 molecule.
These results demonstrate the possible therapy for severe bacterial infectious diseases by blockade or modulation of cytokine cascade. Especially, it is emphasized that the specific blockade of endogenous IFN-gamma may be an available mean to treat the patients who suffered from the severe MRSA infection.
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