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白细胞介素-9在哮喘和过敏反应中的作用

[Role of interleukin-9 in asthma and allergic reactions].

作者信息

Renauld J-C

机构信息

Ludwig Institute for Cancer Research, Brussels Branch, de Duve Institute, UCL.

出版信息

Bull Mem Acad R Med Belg. 2007;162(5-6):275-82; discussion 283-5.

Abstract

Interleukin 9 (IL-9) is a cytokine produced by activated T lymphocytes and that activates in vitro mast cells as well as T and B lymphocytes. In vivo, transgenic mice overexpressing the gene encoding IL-9 show several of the hallmarks of human allergic asthma: increased IgE concentration, bronchial mastocytosis, eosinophilia, increased mucus production, as well as bronchial hyperresponsiveness. Whereas some of these features reflect direct IL-9 activities on target cells such as mast cells and B lymphocytes, increased mucus production and eosinophilia rather result from IL-13 and IL-5 production induced by IL-9 in T lymphocytes and mast cells. Preclinical studies in mice have shown that anti-IL-9 blocking antibodies interfere with the development of asthma-like reactions. In the human species, asthmatic patients produce large amounts of this cytokine and IL-9 production correlates nicely with species biological parameters of the disease. Phase 2 clinical trials are in progress to test the efficacy of anti-IL-9 antibodies in humans.

摘要

白细胞介素9(IL-9)是一种由活化的T淋巴细胞产生的细胞因子,它能在体外激活肥大细胞以及T和B淋巴细胞。在体内,过度表达编码IL-9基因的转基因小鼠表现出人类过敏性哮喘的一些特征:IgE浓度增加、支气管肥大细胞增多、嗜酸性粒细胞增多、黏液分泌增加以及支气管高反应性。虽然这些特征中的一些反映了IL-9对肥大细胞和B淋巴细胞等靶细胞的直接作用,但黏液分泌增加和嗜酸性粒细胞增多更多是由IL-9在T淋巴细胞和肥大细胞中诱导产生的IL-13和IL-5所致。小鼠的临床前研究表明,抗IL-9阻断抗体可干扰哮喘样反应的发展。在人类中,哮喘患者会产生大量这种细胞因子,且IL-9的产生与该疾病的生物学参数密切相关。目前正在进行2期临床试验以测试抗IL-9抗体在人体中的疗效。

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