Bradding P, Feather I H, Wilson S, Holgate S T, Howarth P H
University Medicine, Southampton General Hospital, United Kingdom.
Am J Respir Crit Care Med. 1995 Jun;151(6):1900-6. doi: 10.1164/ajrccm.151.6.7767538.
Seasonal allergic rhinitis is characterized by the development of nasal mucosal inflammation in response to natural allergen exposure, and is prevented by the administration of topical corticosteroids. Interleukin-4 (IL-4), IL-5, and IL-6 may have important roles in this process, and in vitro the gene transcription for each of these cytokines is inhibited by corticosteroids. In this study we have therefore investigated the effect of seasonal allergen exposure on the expression of immunoreactivity for IL-4, IL-5, and IL-6 in nasal mucosal biopsies, and the effect of regular prophylactic treatment with the topical corticosteroid, fluticasone propionate. Following a nasal mucosal biopsy out of season, patients were randomized double-blind to receive 6 wk of treatment during the pollen season with either topical fluticasone nasal spray (200 micrograms daily) or matching placebo. Each subject underwent a repeat nasal biopsy at the end of the 6-wk treatment period. Seasonal increases in epithelial eosinophils (p = 0.046), submucosal eosinophils (p = 0.001), and epithelial mast cells (p = 0.055) occurred in the placebo--but not the fluticasone-treated patients. Submucosal mast cell numbers did not change in either group. Immunoreactivity for IL-4 and IL-6 was localized predominantly to mast cells while IL-5 was found in both mast cells and eosinophils. Numbers of IL-4+ cells in the nasal submucosa were significantly suppressed by treatment with fluticasone (p = 0.0003 for monoclonal antibody [mAb] 3H4, p = 0.041 for mAb 4D9). In contrast, fluticasone treatment failed to influence the number of IL-5 and IL-6 immunoreactive cells.(ABSTRACT TRUNCATED AT 250 WORDS)
季节性变应性鼻炎的特征是鼻黏膜炎症在接触天然变应原后发生,局部使用糖皮质激素可预防该病。白细胞介素-4(IL-4)、IL-5和IL-6可能在此过程中发挥重要作用,在体外,这些细胞因子的基因转录均受到糖皮质激素的抑制。因此,在本研究中,我们调查了季节性变应原暴露对鼻黏膜活检组织中IL-4、IL-5和IL-6免疫反应性表达的影响,以及局部使用糖皮质激素丙酸氟替卡松进行常规预防性治疗的效果。在非花粉季节进行鼻黏膜活检后,患者被随机双盲分组,在花粉季节接受为期6周的治疗,分别使用局部丙酸氟替卡松鼻喷雾剂(每日200微克)或匹配的安慰剂。在6周治疗期结束时,每位受试者均接受重复鼻活检。安慰剂组患者的上皮嗜酸性粒细胞(p = 0.046)、黏膜下嗜酸性粒细胞(p = 0.001)和上皮肥大细胞(p = 0.055)出现季节性增加,而丙酸氟替卡松治疗组患者未出现。两组患者的黏膜下肥大细胞数量均未改变。IL-4和IL-6的免疫反应性主要定位于肥大细胞,而IL-5则在肥大细胞和嗜酸性粒细胞中均有发现。丙酸氟替卡松治疗可显著抑制鼻黏膜下IL-4+细胞数量(单克隆抗体[mAb]3H4,p = 0.0003;mAb 4D9,p = 0.041)。相比之下,丙酸氟替卡松治疗未能影响IL-5和IL-6免疫反应性细胞的数量。(摘要截短至250字)