Robinson D S, Ying S, Bentley A M, Meng Q, North J, Durham S R, Kay A B, Hamid Q
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, United Kingdom.
J Allergy Clin Immunol. 1993 Sep;92(3):397-403. doi: 10.1016/0091-6749(93)90118-y.
We recently demonstrated that T lymphocytes in bronchoalveolar lavage (BAL) fluid from atopic asthmatic patients were activated and expressed increased cytokine messenger ribonucleic acid (mRNA) for "TH2-type" cytokines, particularly IL-4 and IL-5, when compared with those in normal control subjects. This pattern of cytokines may determine the nature of the cellular infiltrate in the bronchial mucosa in asthma and hence the bronchial hyperresponsive (BHR) and symptoms that characterize this condition.
To examine the association between these cytokines and clinical measures of asthma severity we have extended our studies of BAL cells from subjects with atopic asthma. Numbers of BAL cells with positive in situ hybridization signals for IL-2, IL-3, IL-4, IL-5, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon-gamma were counted on cytocentrifuge preparations. Results were compared between patients with symptomatic (n = 19) and asymptomatic asthma (n = 10), and associations were sought with airway methacholine responsiveness, resting airway caliber, and asthma symptom scores.
There were increased proportions of cells positive for IL-3 (p < 0.05), IL-4 (p < 0.005), IL-5 (p < 0.005), and GM-CSF (p < 0.005) mRNA in BAL fluid from patients with symptomatic asthma when compared with that from subjects free of symptoms, but no difference between the groups in numbers of cells expressing IL-2 and interferon-gamma mRNA. There were significant associations among numbers of cells expressing mRNA for IL-4, IL-5, and GM-CSF, and airflow restriction, BHR, and Aas asthma score.
These findings support the hypothesis that cytokines contribute to airway events that determine asthma symptoms and BHR.
我们最近证实,与正常对照受试者相比,特应性哮喘患者支气管肺泡灌洗(BAL)液中的T淋巴细胞被激活,且“TH2型”细胞因子,尤其是IL-4和IL-5的细胞因子信使核糖核酸(mRNA)表达增加。这种细胞因子模式可能决定哮喘患者支气管黏膜中细胞浸润的性质,进而决定这种疾病所特有的支气管高反应性(BHR)和症状。
为了研究这些细胞因子与哮喘严重程度临床指标之间的关联,我们扩大了对特应性哮喘患者BAL细胞的研究。在细胞离心涂片上,对白细胞介素-2(IL-2)、IL-3、IL-4、IL-5、粒细胞巨噬细胞集落刺激因子(GM-CSF)和干扰素-γ原位杂交信号阳性的BAL细胞数量进行计数。比较有症状哮喘患者(n = 19)和无症状哮喘患者(n = 10)的结果,并寻找与气道对乙酰甲胆碱的反应性、静息气道口径和哮喘症状评分之间的关联。
与无症状受试者相比,有症状哮喘患者BAL液中IL-3(p < 0.05)、IL-4(p < 0.005)、IL-5(p < 0.005)和GM-CSF(p < 0.005)mRNA阳性细胞的比例增加,但两组之间表达IL-2和干扰素-γ mRNA的细胞数量没有差异。表达IL-4、IL-5和GM-CSF mRNA的细胞数量与气流受限、BHR和哮喘评分之间存在显著关联。
这些发现支持细胞因子促成决定哮喘症状和BHR的气道事件这一假说。