Tang C, Rolland J M, Ward C, Quan B, Walters E H
Dept of Respiratory Medicine, Alfred Hospital, Prahran, Victoria, Australia.
Eur Respir J. 1997 Mar;10(3):624-32.
There is increasing evidence to suggest a key role for interleukin-5 (IL-5) in the regulation of airway eosinophilia in asthma. We compared the capacity for IL-5 production in atopic asthmatic, nonatopic asthmatic, atopic nonasthmatic and normal subjects, and evaluated the usefulness of peripheral blood cells for reflecting airway cell reactivity. Bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMC) from 12 atopic and 10 nonatopic asthmatics (without inhaled steroid therapy), 9 atopic nonasthmatics, and 10 normal controls were cultured with or without house dust mite (HDM, 10 microg x mL-1) stimulation. CD4+ T-cell activation, IL-5 and interferon-gamma (IFN-gamma) production in the cultures were assessed. Both for BAL and PBMC samples, atopic and nonatopic asthmatic subjects showed comparable spontaneous production of IL-5, which was significantly higher than that either for atopic nonasthmatics or normal controls (p<0.05 or p<0.01). There was a significant correlation between the percentage of eosinophils in BAL and spontaneous production of IL-5 by BAL cells in both asthmatic groups (p<0.05 or p<0.01). Both these parameters were also associated with asthmatic airway narrowing as denoted by a negative relationship with baseline forced expiratory volume in one second (FEV1) as percentage predicted (p<0.05 and p<0.01, respectively). In contrast, IFN-gamma production by unstimulated BAL cells from normal controls was higher than that for BAL cell cultures of nonatopic asthmatic subjects (p<0.05). Following HDM stimulation, both atopic groups had comparable positive responses in terms of CD4+ T-cell activation, but there was relatively greater IL-5 production in asthmatic PBMC (p<0.05) and, in particular, BAL cell cultures (p<0.01). These findings suggest that elevated IL-5 production is a common feature of BAL cells and PBMC in atopic and nonatopic asthma. In addition, atopic asthmatics show greater IL-5 production in response to specific allergen compared with atopic nonasthmatics, an effect most marked in BAL cells compared to PBMC. Hence, peripheral blood mononuclear cells can reflect cytokine immunoreactivity of airway cells, but lack local cellular interactions, which limits their usage in asthma research.
越来越多的证据表明,白细胞介素-5(IL-5)在哮喘气道嗜酸性粒细胞增多的调节中起关键作用。我们比较了特应性哮喘患者、非特应性哮喘患者、特应性非哮喘患者和正常受试者产生IL-5的能力,并评估了外周血细胞反映气道细胞反应性的实用性。将12例特应性哮喘患者和10例非特应性哮喘患者(未接受吸入类固醇治疗)、9例特应性非哮喘患者和10例正常对照者的支气管肺泡灌洗(BAL)细胞和外周血单核细胞(PBMC)在有或无屋尘螨(HDM,10μg/mL)刺激的情况下进行培养。评估培养物中CD4+T细胞活化、IL-5和干扰素-γ(IFN-γ)的产生。对于BAL和PBMC样本,特应性和非特应性哮喘患者的IL-5自发产生水平相当,均显著高于特应性非哮喘患者或正常对照者(p<0.05或p<0.01)。在两组哮喘患者中,BAL中嗜酸性粒细胞百分比与BAL细胞IL-5自发产生之间存在显著相关性(p<0.05或p<0.01)。这两个参数也与哮喘气道狭窄相关,表现为与预测的一秒用力呼气容积(FEV1)基线百分比呈负相关(分别为p<0.05和p<0.01)。相比之下,正常对照者未刺激的BAL细胞产生的IFN-γ高于非特应性哮喘患者的BAL细胞培养物(p<0.05)。在HDM刺激后,两组特应性患者在CD4+T细胞活化方面的阳性反应相当,但哮喘患者的PBMC(p<0.05),尤其是BAL细胞培养物(p<0.01)中IL-5产生相对更多。这些发现表明,IL-5产生增加是特应性和非特应性哮喘中BAL细胞和PBMC的共同特征。此外,与特应性非哮喘患者相比,特应性哮喘患者对特定过敏原的IL-5产生更多,与PBMC相比,这种效应在BAL细胞中最为明显。因此,外周血单核细胞可以反映气道细胞的细胞因子免疫反应性,但缺乏局部细胞间相互作用,这限制了它们在哮喘研究中的应用。