2022 Fiscal Year Final Research Report
Immunomodulatory effects of biologics for asthma.
| Project/Area Number |
20K08549
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 気管支喘息 / 生物学的製剤 / 好酸球 / タイプ２炎症 / 免疫調節 |
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| Outline of Final Research Achievements |
In this study, the immunomodulatory effects of biologics for severe asthma patients in vivo were analyzed with a focus on peripheral blood lymphocyte fractions. The results of one year of treatment with each of mepolizumab, benralizumab, and dupilumab showed different behavior of peripheral blood lymphocytes in each. Each also showed differences in factors predicting the effectiveness of patients. Each formulation has different mechanisms - IL-5 inhibition, induction of apoptosis in eosinophils, and IL-4/IL-13 inhibition, respectively - and these differences may be reflected in their different in vivo effects. Clarification of these differences is expected to elucidate the mechanisms constituting asthma pathology and elucidate the functions of eosinophils and cytokines in the human organism.
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| Free Research Field |
呼吸器内科
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| Academic Significance and Societal Importance of the Research Achievements |
メポリズマブとベンラリズマブは好酸球を標的とした製剤である。前者はタイプ2炎症マーカーが高く、非タイプ2炎症マーカーが低い症例でより有効であった可能性がある。一方、後者は非タイプ2炎症を司るTh17細胞が多い症例でより有効であった可能性が示唆された。Th17のTh2炎症への修飾はTh2炎症を増強し、ステロイド抵抗性を付与する可能性がある。生物学的製剤の適応のある喘息症例はステロイド抵抗性を有していることが多く、この結果は、生物学的製剤のステロイド抵抗性改善効果について解析を進める契機となった。ステロイド抵抗性喘息の克服はすなわち喘息の克服にほかならず、この目標に向けてさらなる研究を実施する。
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