Balding C E, Howie A J, Drake-Lee A B, Savage C O
Renal Immunobiology Laboratory, Division of Medical Sciences, MRC Centre for Immune Regulation, The Medical School, University of Birmingham, Birmingham, UK.
Clin Exp Immunol. 2001 Aug;125(2):332-9. doi: 10.1046/j.1365-2249.2001.125002332.x.
Wegener's granulomatosis initially affects upper respiratory tract organs including the nasal mucosa in more than 90% of patients. The inflammation is typically granulomatous with associated vasculitis. T lymphocytes are usually a prominent component of the leucocyte infiltrate. Previous studies using peripheral blood T cells have implicated IFN-gamma rich Th1-type responses. This study addressed the cytokine milieu in nasal mucosa from 10 patients with active Wegener's granulomatosis using immunohistochemistry. Increased levels of CD3+ T cells and eosinophils were present compared with normal and disease controls. There was increased expression of IL-4, down-regulation of IL-2 and no detectable IFN-gamma. There was increased expression of the chemokine receptor CCR3 by infiltrating cells, consistent with an IL-4 dominant, Th2-biased response. In contrast, renal biopsy tissue from 10 patients with active Wegener's granulomatosis showed expression of IL-2 and IL-4. The Th2-type environment within nasal mucosa, often the initial site of disease activity in Wegener's, is consistent with a local allergic response in these patients.
韦格纳肉芽肿病最初累及上呼吸道器官,90%以上的患者包括鼻黏膜。炎症通常为肉芽肿性并伴有血管炎。T淋巴细胞通常是白细胞浸润的主要成分。以往使用外周血T细胞的研究表明存在富含干扰素-γ的Th1型反应。本研究采用免疫组织化学方法研究了10例活动期韦格纳肉芽肿病患者鼻黏膜中的细胞因子环境。与正常对照和疾病对照相比,CD3+ T细胞和嗜酸性粒细胞水平升高。白细胞介素-4表达增加,白细胞介素-2下调,未检测到干扰素-γ。浸润细胞中趋化因子受体CCR3表达增加,与白细胞介素-4占主导、偏向Th2的反应一致。相比之下,10例活动期韦格纳肉芽肿病患者的肾活检组织显示白细胞介素-2和白细胞介素-4表达。鼻黏膜内的Th2型环境通常是韦格纳病疾病活动的初始部位,这与这些患者的局部过敏反应一致。