{"title":"不同类型2型细胞因子对健康人血液嗜酸性粒细胞功能直接影响的差异","authors":"Yutaka Ueda, Kazuyuki Nakagome, Kazuki Katayama, Hidetoshi Iemura, Sachiko Miyauchi, Toru Noguchi, Takehito Kobayashi, Tomoyuki Soma, Toshiko Itazawa, Makoto Nagata","doi":"10.5415/apallergy.0000000000000157","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Eosinophil inflammation often persists in the airways of severe asthmatics, even under treatment with high-dose inhaled corticosteroids. Biologics for various type 2 cytokines have been recently developed for corticosteroid-resistant, eosinophil-dominant, severe asthma. However, it is unclear whether these biologics act directly on eosinophils.</p><p><strong>Objective: </strong>In this study, we examined whether various type 2 cytokines targeted by biologics can directly modify the functions of eosinophils obtained from the peripheral blood of healthy individuals.</p><p><strong>Methods: </strong>Peripheral eosinophils of healthy subjects were purified by conventional negative-depletion methods using anti-CD16 beads to avoid the priming effect (i.e., stimulation <i>in vitro</i>) to the maximum extent possible. Eosinophils were stimulated with interleukin (IL)-4, IL-5, IL-13, or thymic stromal lymphopoietin (TSLP), and eosinophil adhesiveness to recombinant human-intercellular adhesion molecule (ICAM)-1 was evaluated by eosinophil peroxidase assays. The effect of these cytokines on eosinophil superoxide anion (O<sub>2</sub> <sup>-</sup>) generation was evaluated by the superoxide dismutase-inhibitable reduction of cytochrome C. To determine whether eosinophil degranulation was induced, the concentration of eosinophil-derived neurotoxin (EDN) in the supernatant was measured using enzyme-linked immuno sorbent assay.</p><p><strong>Results: </strong>As reported previously, at 100 pM, IL-5 increased eosinophil adhesiveness to ICAM-1, O<sub>2</sub> <sup>-</sup> generation, and EDN release. Conversely, at concentrations up to 10 nM, IL-4, IL-13, and TSLP did not induce eosinophil adhesiveness, O<sub>2</sub> <sup>-</sup> generation, or EDN release.</p><p><strong>Conclusion: </strong>Type 2 cytokines other than IL-5 do not directly affect the functions of eosinophils from healthy individuals when used at clinical concentrations. These findings suggest that eosinophils play little, or no, direct role in the effects of anti-IL-4 receptor α or anti-TSLP antibody on severe asthma.</p>","PeriodicalId":8488,"journal":{"name":"Asia Pacific Allergy","volume":"14 4","pages":"183-190"},"PeriodicalIF":1.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608611/pdf/","citationCount":"0","resultStr":"{\"title\":\"Differences in the direct effects of various type 2 cytokines on functions of blood eosinophils from healthy subjects.\",\"authors\":\"Yutaka Ueda, Kazuyuki Nakagome, Kazuki Katayama, Hidetoshi Iemura, Sachiko Miyauchi, Toru Noguchi, Takehito Kobayashi, Tomoyuki Soma, Toshiko Itazawa, Makoto Nagata\",\"doi\":\"10.5415/apallergy.0000000000000157\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Eosinophil inflammation often persists in the airways of severe asthmatics, even under treatment with high-dose inhaled corticosteroids. Biologics for various type 2 cytokines have been recently developed for corticosteroid-resistant, eosinophil-dominant, severe asthma. However, it is unclear whether these biologics act directly on eosinophils.</p><p><strong>Objective: </strong>In this study, we examined whether various type 2 cytokines targeted by biologics can directly modify the functions of eosinophils obtained from the peripheral blood of healthy individuals.</p><p><strong>Methods: </strong>Peripheral eosinophils of healthy subjects were purified by conventional negative-depletion methods using anti-CD16 beads to avoid the priming effect (i.e., stimulation <i>in vitro</i>) to the maximum extent possible. Eosinophils were stimulated with interleukin (IL)-4, IL-5, IL-13, or thymic stromal lymphopoietin (TSLP), and eosinophil adhesiveness to recombinant human-intercellular adhesion molecule (ICAM)-1 was evaluated by eosinophil peroxidase assays. The effect of these cytokines on eosinophil superoxide anion (O<sub>2</sub> <sup>-</sup>) generation was evaluated by the superoxide dismutase-inhibitable reduction of cytochrome C. To determine whether eosinophil degranulation was induced, the concentration of eosinophil-derived neurotoxin (EDN) in the supernatant was measured using enzyme-linked immuno sorbent assay.</p><p><strong>Results: </strong>As reported previously, at 100 pM, IL-5 increased eosinophil adhesiveness to ICAM-1, O<sub>2</sub> <sup>-</sup> generation, and EDN release. Conversely, at concentrations up to 10 nM, IL-4, IL-13, and TSLP did not induce eosinophil adhesiveness, O<sub>2</sub> <sup>-</sup> generation, or EDN release.</p><p><strong>Conclusion: </strong>Type 2 cytokines other than IL-5 do not directly affect the functions of eosinophils from healthy individuals when used at clinical concentrations. These findings suggest that eosinophils play little, or no, direct role in the effects of anti-IL-4 receptor α or anti-TSLP antibody on severe asthma.</p>\",\"PeriodicalId\":8488,\"journal\":{\"name\":\"Asia Pacific Allergy\",\"volume\":\"14 4\",\"pages\":\"183-190\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608611/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Asia Pacific Allergy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5415/apallergy.0000000000000157\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asia Pacific Allergy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5415/apallergy.0000000000000157","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ALLERGY","Score":null,"Total":0}
Differences in the direct effects of various type 2 cytokines on functions of blood eosinophils from healthy subjects.
Background: Eosinophil inflammation often persists in the airways of severe asthmatics, even under treatment with high-dose inhaled corticosteroids. Biologics for various type 2 cytokines have been recently developed for corticosteroid-resistant, eosinophil-dominant, severe asthma. However, it is unclear whether these biologics act directly on eosinophils.
Objective: In this study, we examined whether various type 2 cytokines targeted by biologics can directly modify the functions of eosinophils obtained from the peripheral blood of healthy individuals.
Methods: Peripheral eosinophils of healthy subjects were purified by conventional negative-depletion methods using anti-CD16 beads to avoid the priming effect (i.e., stimulation in vitro) to the maximum extent possible. Eosinophils were stimulated with interleukin (IL)-4, IL-5, IL-13, or thymic stromal lymphopoietin (TSLP), and eosinophil adhesiveness to recombinant human-intercellular adhesion molecule (ICAM)-1 was evaluated by eosinophil peroxidase assays. The effect of these cytokines on eosinophil superoxide anion (O2-) generation was evaluated by the superoxide dismutase-inhibitable reduction of cytochrome C. To determine whether eosinophil degranulation was induced, the concentration of eosinophil-derived neurotoxin (EDN) in the supernatant was measured using enzyme-linked immuno sorbent assay.
Results: As reported previously, at 100 pM, IL-5 increased eosinophil adhesiveness to ICAM-1, O2- generation, and EDN release. Conversely, at concentrations up to 10 nM, IL-4, IL-13, and TSLP did not induce eosinophil adhesiveness, O2- generation, or EDN release.
Conclusion: Type 2 cytokines other than IL-5 do not directly affect the functions of eosinophils from healthy individuals when used at clinical concentrations. These findings suggest that eosinophils play little, or no, direct role in the effects of anti-IL-4 receptor α or anti-TSLP antibody on severe asthma.
期刊介绍：
Asia Pacific Allergy (AP Allergy) is the official journal of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI). Although the primary aim of the journal is to promote communication between Asia Pacific scientists who are interested in allergy, asthma, and clinical immunology including immunodeficiency, the journal is intended to be available worldwide. To enable scientists and clinicians from emerging societies appreciate the scope and intent of the journal, early issues will contain more educational review material. For better communication and understanding, it will include rational concepts related to the diagnosis and management of asthma and other immunological conditions. Over time, the journal will increase the number of original research papers to become the foremost citation journal for allergy and clinical immunology information of the Asia Pacific in the future.
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