Kakinoki Y, Ohashi Y, Nakai Y, Washio Y, Nasako Y, Tanaka A, Nakai Y
Department of Otolaryngology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno, Osaka 545-8585, Japan.
Scand J Immunol. 2000 Feb;51(2):202-8. doi: 10.1046/j.1365-3083.2000.00660.x.
The primary aim of this study was to investigate whether the allergen-induced synthesis of cytokines by peripheral blood mononuclear cells (PBMCs) obtained immediately before the pollen season could predict the clinical efficacy of immunotherapy during the following pollen season. PBMCs (1.0 x 106 cells/ml) were obtained from 17 nonatopic subjects and from 60 patients receiving immunotherapy for seasonal allergic rhinitis (caused by Japanese cedar pollens) immediately before the pollen season of 1998, and were cultured for 24 h in the presence of 10 mg/ml of Cry j 1, a major allergen of Japanese cedar pollens, at 37 degrees C in a fully humidified 5% CO2 atmosphere. Total cellular RNA was extracted from the PBMCs, and the allergen-induced interleukin (IL)-4, IL-5 and interferon-gamma (IFN-gamma) mRNA expression was determined using a reverse transcription-polymerase chain reaction. According to the nasal symptoms during the pollen season of 1998, the 60 patients on immunotherapy were divided into 36 good responders (who had no nasal symptoms and no requirement for rescue medications) and 24 poor responders who needed rescue medications to control nasal symptoms. Neither IL-4 mRNA nor IL-5 mRNA was expressed in any of the 17 nonatopic individuals. By contrast, IL-4 mRNA was expressed in 26 good responders and in 22 poor responders, and IL-5 mRNA was expressed in eight good responders (22.2%) and in 23 poor responders (95.8%). IFN-gamma mRNA was expressed in four nonatopic subjects, in nine good responders and in seven poor responders. The expression of IFN-gamma did not differ significantly among the nonatopic subjects, the good responders and the poor responders. The mRNA expression of IL-5 (P < 0.0001), but not of IL-4 (P = 0.0999) and IFN-gamma (P = 0. 7713), differed significantly between the good and poor responders. Therefore, our study has highlighted that positive expression of IL-5 mRNA in PBMCs sampled immediately before the pollen season could be predictive of a poor clinical outcome of immunotherapy during the following pollen season and that the down-regulation of IL-5 mRNA expression in PBMCs could be an important mechanism of pollen immunotherapy related to the clinical efficacy.
本研究的主要目的是调查在花粉季节开始前即刻获取的外周血单个核细胞（PBMC）经变应原诱导后细胞因子的合成情况，能否预测接下来花粉季节免疫治疗的临床疗效。于1998年花粉季节开始前即刻，从17名非特应性个体以及60名接受季节性变应性鼻炎（由日本雪松花粉引起）免疫治疗的患者中获取PBMC（1.0×10⁶细胞/ml），并将其在含有10mg/ml日本雪松花粉主要变应原Cry j 1的条件下，于37℃、5%二氧化碳饱和湿度的环境中培养24小时。从PBMC中提取总细胞RNA，采用逆转录 - 聚合酶链反应测定变应原诱导的白细胞介素（IL）-4、IL-5和干扰素 -γ（IFN-γ）mRNA表达。根据1998年花粉季节期间的鼻部症状，将60名接受免疫治疗的患者分为36名良好反应者（无鼻部症状且无需使用急救药物）和24名需要使用急救药物来控制鼻部症状的不良反应者。17名非特应性个体中均未检测到IL-4 mRNA和IL-5 mRNA表达。相比之下，26名良好反应者和22名不良反应者中检测到IL-4 mRNA表达，8名良好反应者（22.2%）和23名不良反应者（95.8%）中检测到IL-5 mRNA表达。4名非特应性个体、9名良好反应者和7名不良反应者中检测到IFN-γ mRNA表达。非特应性个体、良好反应者和不良反应者之间IFN-γ的表达无显著差异。良好反应者与不良反应者之间，IL-5（P < 0.0001）的mRNA表达存在显著差异，而IL-4（P = 0.0999）和IFN-γ（P = 0.7713）的mRNA表达无显著差异。因此，我们的研究强调，在花粉季节开始前即刻采集的PBMC中IL-5 mRNA的阳性表达可能预示着接下来花粉季节免疫治疗的临床效果不佳，且PBMC中IL-5 mRNA表达的下调可能是与临床疗效相关的花粉免疫治疗的重要机制。
