1999 Fiscal Year Final Research Report Summary
IL-18 deficiency selectively enhances allergen-induced eosinophilia in mice.
| Project/Area Number |
10670567
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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 |
Respiratory organ internal medicine
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
NISHIOKA Yasuhiro 5th Dep of Int Med., Hyogo College of Medicine, Assistant Prof., 医学部, 助手 (60228161)
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| Co-Investigator(Kenkyū-buntansha) |
NAMANISHI Kenji Depatrment of Immunology and Medical Zoology, Prof., 医学部, 教授 (60172350)
OKAMURA Haruki Laboratory of Host Defenses Insitute for Advanced Medical Sciences, Prof., 医学部, 教授 (60111043)
MATSUYAMA Tomohiro 5th Dep of Int Med., Hyogo College of Medicine, Assistant Prof., 医学部, 講師 (10219529)
SUGITA Minoru 5th Dep of Int Med., Hyogo College of Medicine, Prof., 医学部, 教授 (90068429)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Bronchial asthma / IL-18 / Apoptosis / Eosinophil / Fas-Ligand |
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| Research Abstract |
Th2 cytokines are associated with airway inflammation and hyperreactivity in bronchial asthma, and restoration of Th1/Th2 imbalance is a potential avenue for novel therapies. IL-18 is a cytokine secreted by activated macrophages that induces IFN-g production in T1-type cells. We studies a model of allergic asthma in IL-18-deficient mice to investigate the modulatory role of IL-18 on induction and maintenance of Th2 mucosal immunity. In IL-18-deficient mice, levels of eosinophilia and lung damage were significantly higher than in wild-type C57/B6 littermates. Intrapertioneal administration of rIL-18 in deficient mice, reduced these antigen-induced changes to levels seen in wild-type mice, in association with a decrease in IL-4 in bronchoalveolar lavage fluid and lung tissue. However, administration of rIL-18 did not affect IFN-g level and somewhat enhanced the production of IL-5. Notably, reconstitution with rIL-18 increased the numbers of cells staining for Fas ligand (Fas-L) as well as apoptotic cells stained by nick end-labeling in bronchial submucosa infiltrates. These findings indicate that, in vivo, IL-18 not only inhibited antigen-specific Th2 development but also affected apoptosis via Fas/Fas-L interactions. Apparently as a consequence, IL-18 limited the development of local inflammatory response to antigen.
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