1994 Fiscal Year Final Research Report Summary
MECHANISM OF PATHOGENESIS OF LATE-PHASE ASTHMATIC RESPONSE (LAR) : PREVENTIVE EFFECT OF ANTI-IL-5 ANTIBODY ON LAR IN ANIMAL MODEL
| Project/Area Number |
05557023
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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 |
Immunology
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
TAKATSU Kiyoshi INST.MED.SCI., UNIV.TOKYO.PROFESSOR, 医科学研究所, 教授 (10107055)
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| Co-Investigator(Kenkyū-buntansha) |
KARIYONE Al INST.MED.SCI., UNIV.TOKYO,RESEARCH ASSOCIATE, 医科学研究所, 教務職員 (50114450)
AKUTSU Ikuo DOKKYO MEDICAL SCHOOL,LECTURER, アレルギー内科, 助手 (90184126)
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| Project Period (FY) |
1993 – 1994
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| Keywords | type I allergy / Late-phase asthmatic response / Eosinophil / IL-5 / Anti-IL-5 mAb / Hyperreactivity in the airways / Guinea pig model |
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| Research Abstract |
Interleukin 5 (IL-5) induces proliferation and differentiation of eosinophils by interacting with its receptor (IL-5R) which consists of two distinct polypeptide chains, alpha and beta (betac). The IL-5Ralpha alone binds IL-5 with low affinity. The betac does not bind IL-5 by itself, but does form a high affinity IL-5R in combination with IL-5Ralpha.
In this project, an animal model of local allergen (airways) sensitization was employed to study the effects of anti-IL-5 mAb on infiltration of eosinophils into inflammatory region, the development of antigen-induced late asthmatic response (LAR) and the increased bronchial responsiveness following LAR.Guinea pigs exposed aerosolized ovalbumin (OVA) daily for 10 days developed increase in the number of eosinophils in the tracheal wall 24 hr after aerosolized OVA challenge. Furthermore, all animals developed apparent LAR determined by the response with a two-fold increase in respiratory resistance and showed an increase in bronchial responsiveness to acetycholine 24 hr after OVA challenge. In animals treated with anti-IL-5 mAb, however, eosinophil number in the tracheal wall dramatically decreased compared with animals treated with control antibody. The development of LAR was also remarkably suppressed by anti-IL-5 mAb treatment, although similar magnitude of immediate bronchoconstriction was observed. Moreover, in anti-IL-5 antibody treated guinea pigs, an increase in bronchial responsiveness to acetylcholine significantly decreased. The data demonstrate that IL-5 is involved in airway eosinophilia, development of LAR and an increase in bronchial responsiveness induced by allergen sensitization via the airways. Development of IL-5 synthesis inhibitors and/or receptor antagonists could provide another therapeutic class of anti-asthmatic drugs.
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