2002 Fiscal Year Final Research Report Summary
Roles of interleukin-18 in the regulation of inflammatory responses
| Project/Area Number |
13470040
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
OKAMURA Haruki Hyogo College of Medicine, Faculty of medicine, professor, 医学部, 教授 (60111043)
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| Co-Investigator(Kenkyū-buntansha) |
UEDA Haruyasu Hyogo College of Medicine, Faculty of medicine, research associate, 医学部, 助手 (10330458)
KASHIWAMURA Shin-ichirou Hyogo College of Medicine, Faculty of medicine, assistant professor, 医学部, 講師 (00185761)
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| Project Period (FY) |
2001 – 2002
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| Keywords | interleukin-18 / IFN-γ / nitric oxide / inflammation / regulation / Th1 / Th2 / leucocytes / tissue injury |
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| Research Abstract |
Interleukin-18(IL-18) has been shown to be involved in the regulatory mechanism for inflammatory responses. We have shown that IL-18 together with IL-12 strongly induce IFN-γ resulting in production of injurious molecule such as TNFα, nitric oxide, and reactive oxigen species, while in the absence of IL-12, it induces anti-inflammatory cytokines such as IL-4, -5, -10 and -13(Ann.Rev.Immunology, 2001). Thus, IL-18 is considered to be involved in both destructive and compensatory reactions in the inflammatory responses. We have tried to further clarify the roles of IL-18 in the regulatory mechanism for inflammatory responses. IL-18, when singly given to mice, markedly reduces number of circulating leucocytes (Clin.Diagn.Lab.Immunol.2002), while continuous administration causes neutrophilia and eosinophilia (Blood, 2001). The combined administration of IL-12 and IL-18 causes injury in multiple organs and this is due to the excessive production of nitric oxide and to the severe damage in the micro vascular system (J.Interferon cytokine res., 2003). However, we have observed that extraordinarily high levels of TNFα is induced in IL-18 deficient mice, and the bleomycin-induced pneumonia and cerulein-induced pancreatitis are much severe in IL-18 KO mice than in wild type mice (in preparation). Thus, IL-18 plays crucial roles in the tissue injury as well as in the regulation of it. However, we have not yet clarified the mechanism for induction of anti-inflammatory, Th2 type cytokines induced by IL-18. We are now seeking for the regulatory cells induced by IL-18.
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