Humbert M, Corrigan C J, Kimmitt P, Till S J, Kay A B, Durham S R
Allergy and Clinical Immunology, Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom.
Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):704-8. doi: 10.1164/ajrccm.156.3.9610033.
Atopic asthma is characterized by chronic inflammation of the bronchial mucosa in which eosinophil- and immunoglobulin E (IgE)-dependent mechanisms are believed to be prominent. Therefore, specific proeosinophilic mediators such as interleukin (IL)-5 and essential cofactors for IgE switching in B-lymphocytes such as IL-4 could play a pivotal role in asthma. However, the exact role that individual inflammatory mediators play in the development of the disease in humans is still unknown. Using semiquantitative reverse transcriptase-polymerase chain reaction amplification in bronchial biopsies from 10 atopic asthmatics, we have tested the hypothesis that IL-4 and IL-5 mRNA expression relative to beta-actin mRNA correlates with validated indicators of disease severity. IL-4 and IL-5 mRNA copies relative to beta-actin mRNA were detected in bronchial biopsies from atopic asthmatics. The numbers of IL-5 mRNA copies relative to beta-actin mRNA correlated with disease severity assessed by the Aas asthma score (r = 0.70, p = 0.01), baseline FEV1 (r = -0.94, p = 0.001), baseline peak expiratory flow rate (r = -0.77, p = 0.01), peak expiratory flow rate variability over 2 wk (r = 0.69, p = 0.028), and the histamine PC20 (r = -0.72, p = 0.018). Conversely, the numbers of IL-4 mRNA copies relative to beta-actin mRNA did not correlate with asthma severity, but they positively correlated with total serum IgE concentrations (r = -0.90, p = 0.001). Our present results support the concept that IL-5 may determine asthma clinical expression and severity, and by inference they support the development of IL-5 targeted therapies.
特应性哮喘的特征是支气管黏膜的慢性炎症，其中嗜酸性粒细胞和免疫球蛋白E（IgE）依赖性机制被认为是主要的。因此，特定的嗜酸性粒细胞生成介质如白细胞介素（IL）-5以及B淋巴细胞中IgE转换所必需的辅助因子如IL-4可能在哮喘中起关键作用。然而，个体炎症介质在人类疾病发展中的确切作用仍不清楚。通过对10例特应性哮喘患者的支气管活检组织进行半定量逆转录聚合酶链反应扩增，我们检验了以下假设：相对于β-肌动蛋白mRNA，IL-4和IL-5 mRNA的表达与已验证的疾病严重程度指标相关。在特应性哮喘患者的支气管活检组织中检测到相对于β-肌动蛋白mRNA的IL-4和IL-5 mRNA拷贝数。相对于β-肌动蛋白mRNA的IL-5 mRNA拷贝数与通过阿斯哮喘评分评估的疾病严重程度相关（r = 0.70，p = 0.01）、基线第一秒用力呼气容积（FEV1）（r = -0.94，p = 0.001）、基线呼气峰值流速（r = -0.77，p = 0.01）、2周内呼气峰值流速变异性（r = 0.69，p = 0.028）以及组胺PC20（r = -0.72，p = 0.018）。相反，相对于β-肌动蛋白mRNA的IL-4 mRNA拷贝数与哮喘严重程度无关，但与血清总IgE浓度呈正相关（r = -0.90，p = 0.001）。我们目前的结果支持IL-5可能决定哮喘临床表现和严重程度这一概念，据此推断，它们支持开发针对IL-5的治疗方法。
