Wilson D R, Nouri-Aria K T, Walker S M, Pajno G B, O'Brien F, Jacobson M R, Mackay I S, Durham S R
Department of Upper Respiratory Medicine, Imperial College School of Medicine at The National Heart and Lung Institute, Dovehouse St., London, SW3 6LY, UK.
J Allergy Clin Immunol. 2001 Jun;107(6):971-6. doi: 10.1067/mai.2001.115483.
Tissue eosinophilia and infiltration by T(H)2-type T cells are characteristic features of allergic rhinitis both after allergen challenge and during natural allergen exposure. Specific immunotherapy inhibits allergen-induced nasal eosinophilia.
We sought to assess, in the context of a randomized trial, the relationships between symptomatic improvement after immunotherapy and eosinophil numbers and IL-5 expression in the nasal mucosa during the pollen season.
Nasal biopsy specimens were taken from 37 adults with severe summer hay fever at baseline (out of season) and at peak season after 2 years of treatment with a depot grass pollen extract or placebo. Biopsy specimens were processed for immunohistochemistry by using mAbs against eosinophils (EG2), T cells (CD3), and IL-2 receptor-positive cells (CD25), as well as for in situ hybridization by using a sulfur 35-labeled antisense riboprobe directed against IL-5.
Immunotherapy significantly reduced symptoms (49%, P =.01) and medication requirements (80%, P =.007) compared with placebo. There was a 400% increase (P =.004) in eosinophils during the pollen season in placebo-treated patients, which was inhibited in the immunotherapy group (20% increase, P =.04 between groups). Seasonal increases were also observed for CD25(+) cells (P =.002), CD3(+) cells (P =.02), and IL-5 mRNA-expressing cells (P =.03) in the placebo group but not in the immunotherapy group. A significant correlation was observed between eosinophils and IL-5 expression (r = 0.5, P <.05). Both eosinophils (r = 0.6, P <.02) and IL-5 (r = 0.6, P <.02) correlated with symptoms after immunotherapy.
Improvement in symptoms after grass pollen immunotherapy may result, at least in part, from inhibition of IL-5-dependent tissue eosinophilia during the pollen season.
在变应原激发后以及自然接触变应原期间,组织嗜酸性粒细胞增多及辅助性T细胞2型(TH2)浸润是变应性鼻炎的特征性表现。特异性免疫疗法可抑制变应原诱导的鼻嗜酸性粒细胞增多。
在一项随机试验背景下,我们试图评估免疫疗法后症状改善与花粉季节期间鼻黏膜嗜酸性粒细胞数量及白细胞介素-5(IL-5)表达之间的关系。
对37例重度夏季花粉症成年患者在基线期(非花粉季节)以及接受长效草花粉提取物或安慰剂治疗2年后的花粉季节高峰期进行鼻活检取材。活检标本采用抗嗜酸性粒细胞单克隆抗体(EG2)、抗T细胞单克隆抗体(CD3)及抗IL-2受体阳性细胞单克隆抗体(CD25)进行免疫组织化学处理,同时采用硫35标记的抗IL-5反义核糖探针进行原位杂交。
与安慰剂相比,免疫疗法显著减轻了症状(减轻49%,P = 0.01)并减少了药物需求(减少80%,P = 0.007)。安慰剂治疗患者在花粉季节嗜酸性粒细胞增加了400%(P = 0.004),而免疫疗法组受到抑制(增加20%,组间比较P = 0.04)。安慰剂组CD25(+)细胞(P = 0.002)、CD3(+)细胞(P = 0.02)及表达IL-5 mRNA的细胞(P = 0.03)也出现季节性增加,而免疫疗法组未出现。嗜酸性粒细胞与IL-5表达之间存在显著相关性(r = 0.5,P < 0.05)。免疫疗法后嗜酸性粒细胞(r = 0.6,P < 0.02)及IL-5(r = 0.6,P < 0.02)均与症状相关。
草花粉免疫疗法后症状改善可能至少部分是由于在花粉季节抑制了IL-5依赖性组织嗜酸性粒细胞增多。