白细胞介素6对哮喘小鼠气道炎症和上皮下纤维化的影响

目的 :研究白细胞介素 6对哮喘小鼠气道炎症和气道结构重建的作用。方法 :雄性BALB C种系小鼠 2 4只 ,随机分成处理组、模型组和对照组 ,每组 8只 ,用卵蛋白致敏和反复激发 4周。每次激发前处理组腹腔内注射 2 0 0 μg白细胞介素 6单克隆抗体 ,模型组注射 2 0 0 μg大鼠IgG ,对照组注射等量的生理盐水。比较 3组气道反应性 (PC1 2 0 )、支气管肺泡灌洗液细胞成分、基底膜和上皮下胶原层厚度的变化。结果 :卵蛋白反复激发诱发小鼠PC1 2 0 显著降低 ,气道内炎症细胞数量明显增多 ,上皮基底膜增厚和上皮下胶原增加。与模型组比较 ,处理组支气管肺泡灌洗液中巨噬细胞、中性白细胞、嗜酸细胞和淋巴细胞明显上升(P <0 0 5 ) ,基底膜和上皮下胶原厚度分别从 (3 1± 0 4 ) μm和 (4 5± 0 3) μm减少至 (2 2± 0 2 ) μm和 (3 5± 0 2 ) μm(P <0 0 5 ) ,但PC1 2 0 无改变 (P >0 0 5 )。结论 :白细胞介素 6在哮喘中的作用是抑制气道炎症和促进气道结构重建。     

气道上皮IL-25促进哮喘气道重塑

目的:通过检测白细胞介素-25(IL-25)在嗜酸细胞性哮喘(EA)及非嗜酸细胞性哮喘(NEA)患者的血清、诱导痰及气道上皮中的表达,探讨其在支气管哮喘气道重塑中的作用。方法:选取初诊的哮喘患者55例,健康对照组27例,所有受试者均进行肺通气功能检查,然后采集空腹静脉血及诱导痰。据诱导痰中嗜酸性粒细胞(EOS)的比例将哮喘患者分为EA组和NEA组。采用ELISA检测血清及诱导痰中IL-25的水平,同时对其中的10例EA组患者、10例NEA组患者及10例健康对照者行电子支气管镜气道黏膜活检,免疫组织化学技术分析IL-25在气道上皮的表达,HE染色测量气道重塑的重要指标-基底膜厚度,并行血清及诱导痰中IL-25的水平与基底膜平均厚度的相关性分析。结果:与正常对照组相比,EA和NEA组哮喘患者的肺功能轻度受损。ELISA结果显示哮喘患者血清及诱导痰中IL-25的水平明显高于对照组(P<0.05),而EA和NEA组哮喘患者间差异无统计学意义(P>0.05)。免疫组织化学结果显示哮喘患者气道上皮IL-25的表达明显高于对照组,HE染色显示气道黏膜下的基底膜厚度明显增加(P<0.05)。相关性分析显示哮喘患者血清及诱导痰中IL-25水平与气道黏膜下基底膜平均厚度成正相关。结论:IL-25可能有促进哮喘气道重塑的作用,嗜酸性粒细胞与基底膜厚度无明显相关性,其在哮喘气道重塑中的作用可能是有限的。     

比较地塞米松和色甘酸钠对哮喘豚鼠气道重建的作用

观察地塞米松及色甘酸钠对哮喘豚鼠气道重建的干预作用。 2 7只豚鼠随机分为 3组 :(1)哮喘组 :卵清蛋白致敏、激发 8周 ;(2 )激素组和 (3)色甘酸钠组 :分别于实验第 5至 8周给予地塞米松和色甘酸钠。肺功能仪测量肺功能 ,ELISA法检测支气管肺泡灌洗液中转化生长因子 β1及表皮生长因子的含量 ,图像分析系统对豚鼠气道进行形态学测量 ,计数气道壁嗜酸细胞数目。结果显示激素组及色甘酸钠组大气道纤维组织厚度分别为 (9 16± 1 17μm和 8 12± 0 94 μm) ,显著低于哮喘组 (17 0 3± 3 0 7μm) (p <0 0 0 1)。两组的FEV0 3 /FVC分别为 (80 86± 3 14和79 12± 2 93) ,显著高于哮喘组 (73 2 2± 4 5 6 ) (p <0 0 5 )。地塞米松及色甘酸钠均可抑制哮喘豚鼠气道壁纤维组织增生 ,改善肺功能 ,但对平滑肌的肥厚均无明显抑制作用。     

PPD对豚鼠实验性哮喘气道炎症的作用

目的：探索结核菌素纯蛋白衍生物（purified protein derivative,PPD）对豚鼠实验性哮喘气道炎症的作用。方法：实验采用31只豚鼠，体质量250g左右，分为对照组、卵蛋白（ovalbumin,OVA)致敏组和PPD治疗组。用OVA（Ⅲ级）致敏豚鼠复制豚鼠哮喘模型。结果：经过OVA致敏的动物气道支气管肺泡灌洗液（BALF）和肺组织中嗜酸粒细胞以及BALF中白细胞总计数有明显增加，PPD可不同程度地降低肺组织嗜酸粒细胞的气道浸润，并使BALF中炎性细胞总数降低。结论：使用本实验体系PPD可以减轻实验性哮喘的气道炎症反应。     

姜黄素对哮喘大鼠肺组织MMP-9与TIMP-1的表达以及气道重构的影响

目的探讨姜黄素对卵清白蛋白致敏哮喘模型大鼠肺组织基质金属蛋白酶-9(MMP-9)及其组织抑制物-1(TIMP-1)的表达与气道重构的影响。方法 36只清洁级SD雄性大鼠随机分为对照组、哮喘组和姜黄素组,用卵蛋白作为致敏原制备哮喘大鼠模型,对支气管肺泡灌洗液(BALF)细胞总数及嗜酸性粒细胞计数,采用动物呼吸机检测各组大鼠气道呼气阻力,HE染色观察各组大鼠肺组织的病理学变化,采用图像分析软件测定肺组织切片中的支气管壁内周长(Pi)、支气管管壁面积(WAt)、支气管平滑肌面积(WAm),Western blot方法检测各组大鼠肺组织MMP-9与TIMP-1的表达。结果姜黄素干预可显著降低哮喘大鼠BALF中细胞总数及嗜酸粒细胞计数、降低哮喘大鼠肺组织的炎性细胞浸润,降低气道炎症,降低WAt/Pi、WAm/Pi的比值(P0.01);肺功能分析结果显示,姜黄素干预可显著降低哮喘大鼠的呼气阻力(P0.01);Western blot结果显示,姜黄素干预可显著降低哮喘大鼠肺组织MMP-9的表达,上调TIMP-1的表达(P0.01)。结论姜黄素降低哮喘大鼠气道炎症及气道阻力,减轻哮喘气道重构,可能与降低MMP-9的表达,上调TIMP-1的表达相关。     

GATA-3在大鼠哮喘模型气道炎症中作用的实验研究

目的：探讨GATA-3在Wistar大鼠哮喘模型气道炎症中的作用。 方法： 按常用方法复制大鼠哮喘模型并分为哮喘组(A组)，地塞米松治疗组（D组），反义寡核苷酸治疗组（AS组），无意义寡核苷酸治疗组（NS组）和正常对照组（N组）5组，每组10只。反义寡核苷酸和无意义寡核苷酸经鼻气管内给药，地塞米松腹腔注射给药。HE染色方法观察气道炎症变化。免疫组化方法观察GATA-3阳性细胞数。用RT-PCR方法观察大鼠肺组织GATA-3 mRNA表达。用Western 蛋白印迹法检测肺组织中GATA-3蛋白质表达。 结果： A组GATA-3 mRNA和蛋白质的表达量及气道嗜酸性粒细胞浸润数量明显大于N组（P<0.01）。AS组和D组GATA-3 mRNA和蛋白质表达量及气道嗜酸性粒细胞浸润数量均明显低于A组（P<0.01）。NS组GATA-3 mRNA和蛋白质表达量和嗜酸性粒细胞浸润数量与A组相比差异无显著（P>0.05）。GATA-3的表达与大鼠支气管肺组织中嗜酸性粒细胞浸润数量呈正相关，r=0.995(P<0.01)。 结论： GATA-3反义寡核苷酸能特异性地抑制GATA-3基因的表达，减轻气道炎症反应。GATA-3 在Wistar大鼠哮喘模型效应阶段气道炎症中具有重要作用。     

支气管哮喘患者血浆sICAM-1、嗜碱性细胞及嗜酸性细胞的变化及其意义

支气管哮喘是一种以气道高反应性为特点的慢性气道变应性炎症, 此种炎症与T淋巴细胞、嗜碱性细胞及嗜酸性细胞浸润、激活及所释放的细胞因子和介质有关. 近年来研究表明, 这些细胞在血管内流动, 粘附于内皮细胞, 并激活穿过内皮细胞进入气道粘膜层, 与多种趋化因子和粘附分子有关[1].本文着重探讨粘附分子中的重要成份可溶性细胞间粘附分子-1(sICAM-1)在哮喘中的变化以及与嗜碱性细胞和嗜酸性细胞的关系.     

支气管哮喘患儿血清sICAM-1、MMP-9水平与气道炎症、重塑的关系探讨

目的 探讨支气管哮喘患儿血清可溶性细胞间黏附分子-1(sICAM-1)、基质金属蛋白酶-9(MMP-9)水平与气道炎症、重塑的关系.方法 选取2018年2月至2020年9月于本院接受治疗的支气管哮喘患儿62例作为观察组,同期体检健康的40例儿童作为对照组,收集两组血常规资料及外周血2 mL,检测血清sICAM-1、MMP-9水平,采用高分辨率CT扫描肺部并计算气道壁厚度/气道管腔外径(T/D)、气道壁面积占气道总截面积百分比(WA％),分析sICAM-1、MMP-9水平与气道炎症指标、气道重塑的相关性.结果 观察组sICAM-1、MMP-9、嗜酸性粒细胞计数、T/D、WA％显著高于对照组(P<0.01);重度组患儿血清sICAM-1、MMP-9、嗜酸性粒细胞计数、T/D、WA％水平显著高于轻、中度组(P<0.01);哮喘患儿血清sICAM-1与嗜酸性粒细胞计数、T/D、WA％呈线性正相关(r=0.325、0.248、0.356,P<0.01),MMP-9水平与嗜酸性粒细胞计数、T/D、WA％呈线性正相关(r=0.489、0.437、0.572,P<0.01).治疗后,观察组血清sICAM-1、MMP-9显著降低(P<0.01).结论 支气管哮喘患儿血清sICAM-1、MMP-9高于正常水平,与气道炎症及重塑指标具有相关性,可能在炎症进展及气道重塑进程中起到重要作用.     

嗜酸粒细胞凋亡在哮喘发病及治疗中的意义

气道嗜酸粒细胞浸润是支气管哮喘的重要特征之一。本文对影响嗜酸粒细胞凋亡的各种因素进行了综述,分析了通过调控嗜酸粒细胞凋亡,清除募集在气道内的嗜酸粒细胞,消除气道炎症的可行性。     

皮下注射和口服螨制剂脱敏在调节小鼠气道炎症和IgE中作用的比较

为了比较皮下注射和口服螨制剂脱敏在调节小鼠气道炎症和血清IgE中的作用。建立粉尘螨主要过敏原 (Df2 )致BALB/c小鼠气道炎症模型 ,以不同剂量的Df2经皮下注射和口服脱敏 ,检测小鼠支气管肺泡灌洗液 (BALF )中炎症细胞总数及分类、气道炎症细胞浸润程度、小鼠血清总IgE及Df2特异性IgE。结果 :皮下注射组和口服组BALF中炎症细胞总数及嗜酸粒细胞百分比较模型组明显降低 ,气道炎症细胞浸润有所减轻 ,皮下注射组和口服组小鼠血清总IgE均明显降低 ,皮下注射组Df2特异性IgE吸光度值明显降低 ,口服组Df2特异性IgE吸光度值与模型组无明显差异。本实验显示皮下注射和口服脱敏均可减轻该模型小鼠气道炎症细胞浸润 ,皮下注射降低特异性IgE的作用优于口服脱敏。     

Identification of basophils by immunohistochemistry in the airways of post-mortem cases of fatal asthma

There is increasing evidence for the role of basophils in the pathogenesis of bronchial asthma. To examine the presence of basophils in the airways of patients with fatal asthma by immunohistochemistry, we stained lung tissues from four post-mortem cases who had died from severe asthmatic attacks and four controls with a monoclonal antibody raised against tryptase (AA-1) and anti-IgE. Mast cells and basophils were identified in the bronchioles as AA-1- and anti-IgE-positive cells, and anti-IgE-positive cells, respectively. Airway mast cells were found beneath the basement membrane, near blood vessels in the submucosa, and adjacent to the submucosal glands, and scattered throughout the muscle bundles. There was a significant increase of mast cells in the asthma group compared with the control group (203.5+/-84.6/mm2, mean+/-s.d. vs 37.7+/-8.7/mm2, P<0.05, n=4). In contrast, basophils were observed in the airway lumen, in the bronchial epithelium and in the submucosa. The number of basophils in the bronchioles was 81.8+/-55.5/mm2 (n = 4); however, basophils were not found at all in the airways of the control group. Although eosinophils, B lymphocytes and macrophages bear low affinity IgE receptors and could react with anti-IgE, the location of these cells in the close sections did not correspond closely with basophils. The presence of basophils in lung tissues obtained from fatal asthma patients supports the view that basophils play a role in the pathogenesis of bronchial asthma.     

Bronchial inflammation in corticosteroid-sensitive and corticosteroid-resistant asthma at baseline and on oral corticosteroid treatment

BACKGROUND: Pathophysiology of corticosteroid (CS)-resistant asthma remains incompletely understood. OBJECTIVE: To determine if failure of asthma to clinically improve with CS is due to a defective response of airway bronchial inflammation to these drugs. METHODS: Twenty-one asthmatics having a decreased baseline FEV1 that improved >or= 30% with inhaled beta2 agonist got bronchial biopsies before and at the end of an oral CS treatment (methylprednisolone 40 mg daily for 14 days). They were arbitrarily divided into two groups according to baseline FEV1 improvement following this treatment: >or= 23% designated as CS-sensitive (CSS) (n = 10) and < 15% as CS-resistant (CSR) (n = 11). RESULTS: Before oral CS, counts of bronchial mucosa inflammatory cells identified by immunohistochemistry (CD3, MBP, tryptase, CD68, neutrophil elastase and CD25 for lymphocytes, eosinophils, mast cells, macrophages, neutrophils and IL-2 receptors, respectively) were similar in CSS and CSR subjects. Oral CS decreased CD3+ cell counts (medians: 60-20 cells/mm(2); P = 0.014) and MBP+ cell counts (medians: 19-4 cells/mm(2); P = 0.03) in CSS asthmatics, but only tryptase+ cell counts in CSR asthmatics (medians: 30-18 cells/mm(2); P = 0.05). Few bronchial neutrophil elastase+ cells were observed and their counts were similar in the two groups of asthmatics before and when on oral CS (all medians: = 2 cells/mm(2)). CONCLUSIONS: These data show that, in these subjects with moderate to severe asthma, lymphocytes and eosinophils constitute most of the inflammatory cells infiltrating the bronchial mucosa. They also demonstrated that clinical impaired response to CS is associated with a persistent bronchial mucosa cellular infiltrate despite oral CS treatment. Additional studies are required to determine the role of this CS-resistant bronchial inflammation in the impaired asthma clinical response to these drugs.     

Mucosal and systemic inflammatory changes in allergic rhinitis and asthma: a comparison between upper and lower airways

BACKGROUND: Local airway inflammation and airway remodelling are considered important in the clinical expression of allergic asthma. OBJECTIVE: The aim of this study was to compare airway inflammation and remodelling in nasal and bronchial mucosa of subjects with allergic rhinitis with or without asthma. METHODS: Four experimental groups were formed: allergic asthma and rhinitis (n = 19); allergic rhinitis, no asthma (n = 18); atopic subjects, no asthma, no rhinitis (n = 8) and non-allergic healthy control subjects (n = 16). Blood samples, nasal and bronchial biopsy specimens were collected during stable disease. Immunohistochemistry was performed for eosinophils (MBP), mast cells (CD117) and vascular endothelium (CD31). Epithelial loss, reticular basement membrane (RBM) thickness and subepithelial vascularity was assessed with a computer-assisted image analysis system. RESULTS: In nasal and bronchial mucosa, numbers of eosinophils were significantly higher in rhinitis patients with and without asthma than in asymptomatic atopics (P < 0.05) and controls (P < or = 0.01). In bronchial mucosa, the RBM was significantly thickened in rhinitis patients with and without asthma compared to asymptomatic atopics (P < 0.05) and controls (P < 0.01), while in nasal mucosa no differences were seen. Patients with asthma and rhinitis had increased numbers of blood eosinophils (P = 0.05) and skin test reactivity (P = 0.01) compared to patients with rhinitis only. No significant differences could be found between the investigated groups with respect to serum IL-5 and eotaxin levels, the number of mucosal mast cells and the degree of epithelial loss and subepithelial vascularity. Epithelial desquamation was significantly increased in the bronchial mucosa compared to nasal mucosa, not only in asthmatics (P < 0.001), but also in atopics without asthma and rhinitis (P = 0.02). CONCLUSIONS: This study shows that allergic inflammation, increased basement membrane thickness and epithelial desquamation are present in the lower airways of atopic subjects, even before the onset of clinical symptoms. Despite the presence of inflammatory cells, no structural changes could be assessed in nasal mucosa of allergic patients.     

An immunohistochemical study on cellular infiltration of bronchial walls in bronchial asthma]

Inflammatory cell reactions in bronchial asthma have been considered to contribute directly to asthmatic attacks. Therefore, attention has been focused on the role of inflammatory cells in the airway wall. In this study, we investigated inflammatory cells in the airway wall of bronchial asthma histologically and immunohistologically using 20 autopsy cases who died of the asthma attacks (Group A) and 11 autopsy cases who died of other causes (Group B). Six autopsy cases were treated as controls (Group C). A significantly larger number of eosinophils in the bronchi and bronchioles were found in Group A. The majority of eosinophils were found to be stained with EG2. Parts of the bronchial epithelium with marked infiltration of EG2 positive eosinophils were detached from the basal layer. Immunoelectron microscopically, the matrix of EG2 positive areas within the eosinophils corresponded to that of eosinophil granules. A significantly larger number of lymphocytes in the bronchi and bronchioles was observed in Groups A and B. Almost all of these lymphocytes were determined to be activated T lymphocytes. There were significantly more IgE positive cells in cases with bronchial asthma, especially in Group A. The majority of IgE positive cells were determined to be mast cells. These results suggest that eosinophils, lymphocytes and mast cells play an important role in the pathogenesis of bronchial asthma.     

Asthma, inflammation, eosinophils and bronchial hyperresponsiveness

Asthmatics can have a blood eosinophilia which in some studies correlates with the severity of the disease. However, an increased number and percentage of activated eosinophils can be present in the blood without asthma. The eosinophils that contribute to asthma will be those in the lung. In the BAL fluids collected from asthmatics there is usually no change in total cell number, but there are changes in the differential cell count. A consistent finding is an increase in percentage of mast cells and eosinophils with a tendency for an increase in lymphocytes and epithelial cells and a decrease in percentage of macrophages. As with the blood eosinophilia, an increase in number of eosinophils can be present in BAL fluids without asthma. The site of localization and activation of the eosinophils in the lung may be critical. In bronchial biopsies, taken from asthmatics, increased number of mast cells, eosinophils and lymphocytes have been demonstrated in the bronchial mucosa together with shedding of columnar epithelial cells. However these changes have not been found, or have not reached significance, in all studies. An increase in number of activated eosinophils and T-lymphocytes has been demonstrated but an increase in number of degranulating mast cells has been disputed. A consistent finding has been thickening below the basement membrane. Attempts to correlate the changes in the BAL or lung biopsies with the severity of asthma, lung airways function or bronchial responsiveness have given inconsistent results. Treatment of asthmatics with inhaled steroids can reduce the cellular infiltration in the bronchial biopsies to normal levels but this produces a trivial reduction in bronchial responsiveness. It is possible that infiltration of inflammatory cells into the bronchial mucosa is intermittent, at least in mild asthma, but this produces changes leading to a long lasting bronchial hyperresponsiveness.     

Inflammatory biomarkers in airways of patients with severe asthma compared with non-severe asthma

Background About 5–10% of patients with asthma suffer from poorly-controlled disease despite corticosteroid (CS) therapy.
Objective We determined whether there were any differences in inflammatory biomarkers between severe and non-severe asthma patients.
Methods Nineteen severe and 20 non-severe asthma patients were recruited and underwent collection of induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies.
Results Biopsy results showed no differences in eosinophils (major basic protein positive), neutrophils, macrophages, T cells and mast cells in the bronchial submucosa. However, subbasement membrane (SBM) thickness and smooth muscle area were increased in the biopsies. No significant differences were observed in the induced sputum inflammatory cells. In BAL fluid, there was a significant increase in neutrophils but a significant decrease in macrophages. Eosinophil counts were non-significantly increased threefold in both sputum and BAL in severe asthma. Levels of IL-8 and IL-13 in sputum supernatants were similar in both groups of asthma patients. There was a significant inverse correlation between post-bronchodilator forced expiratory volume in 1 s and provocative concentration of methacholine causing a 20% fall in FEV₁ with SBM thickness.
Conclusion Differences in inflammatory cells were observed mainly in terms of increased neutrophils and reduction in macrophage numbers in BAL fluid with a trend towards increased eosinophils in severe asthma compared with non-severe asthma. However, the most notable features are the increase in features of airway wall remodelling of SBM thickness and smooth muscle area.     

Bronchial mast cells are the dominating LTC4S-expressing cells in aspirin-tolerant asthma

The increased bronchial production of leukotriene C4 (LTC4) in asthma is assumed to derive from infiltrating eosinophils expressing LTC4-synthase (LTC4S). Multicolor immunohistofluorescence examination of bronchial cryosections from 30 treated, untreated, or bronchial antigen-provoked aspirin-tolerant individuals with asthma and nine control subjects revealed that the dominating LTC4S-expressing cells were mast cells (> 80%), and not eosinophils. Whereas 95% of the mast cells expressed high levels of LTC4S, only 8-27% of the eosinophils expressed low levels. Image analysis revealed a significantly higher LTC4S expression levels in mast cells than in eosinophils. The bronchial mRNA levels for LTC4S did not correlate with the densities of LTC4S-positive eosinophils or mast cells. Treated individuals with asthma with more than 12% reversibility had significantly higher density of LTC4S-positive mast cells than those with less reversibility, and it correlated significantly with reduction in lung function (FEV1-predicted), both before and after salbutamol inhalation. Thus, mucosal mast cells, and not eosinophils, were the dominating LTC4S-containing cells in both untreated and treated aspirin-tolerant asthma. The density of LTC4S-positive mast cells correlated, moreover, with both the reduction in lung function and the degree of reversibility in treated asthma.     

Localization and upregulation of cysteinyl leukotriene-1 receptor in asthmatic bronchial mucosa

We have tested the hypothesis that the CysLT(1) receptor is expressed by a variety of bronchial mucosal immune cells and that the numbers of these cells increase in asthma, when stable and in exacerbations. We have applied in situ hybridization and immunohistochemistry to endobronchial biopsy tissue to identify and count inflammatory cells expressing CysLT(1) receptor mRNA and protein, respectively, and used double immunohistochemistry to identify the specific cell immunophenotypes expressing the receptor. Double-labeling demonstrated that bronchial mucosal eosinophils, neutrophils, mast cells, macrophages, B-lymphocytes, and plasma cells, but not T-lymphocytes, expressed the CysLT(1) receptor. The numbers of CysLT(1) receptor mRNA and protein positive inflammatory cells in nonsmoking, nonatopic control subjects without asthma were 13 and 16 mm(-2), respectively (median values; n = 15), and were significantly greater in stable asthma (50 and 43 mm(-2), respectively; n = 17; P < 0.001). Compared with stable asthma, there were further significant increases in subjects hospitalized for a severe exacerbation of their asthma (mRNA: median = 113 and protein: 156 mm(-2); n = 15; P < 0.002). For the combined data of both asthma subgroups, there were strong positive correlations between the increased numbers of CD45+ leukocytes and the greater numbers of cells expressing CysLT(1) receptor (mRNA: r = 0.60, P < 0.001; protein: r = 0.73, P < 0.0001). In conclusion, a variety of immunohistologically distinct inflammatory cells express the CysLT(1) receptor in the bronchial mucosa and both these and the total number of leukocytes increase in mild stable disease and increase further when there is a severe exacerbation of asthma.     

哮喘与慢性支气管炎的定量病理学比较研究

目的：探讨哮喘的炎症学说,并比较支气管哮喘与慢性支气管炎气道为症的病理异同。方法：经纤支镜行大气道粘膜活检将１４例哮喘和１３例慢支病人支气管粘膜活检组织以及５例无呼吸病史的意外死亡者尸体听相应部位气道粘膜组织,常规病理切片,进行显微镜下双盲观察,采用多指标的定量病理及统计学处理,进行比较研究。     

Expression of interleukin (IL)-4 and IL-5 proteins in asthma induced by toluene diisocyanate (TDI)

Background TDI-induced asthma exhibits clinical, functional and morphological similarities with allergen-induced asthma, suggesting that an immunological mechanism is involved in the sensitization to TDL In vitro studies using the technique of cloning lymphocytes demonstrated that a great proportion of T-cell clones derived from bronchial mucosa of subjects with TDI-induced asthma produced IL-5 and interferon-gamma, but not IL-4, upon in vitro stimulation. Objectives To investigate in vivo the role of IL-4 and IL-5 on the inflammatory response of the bronchial mucosa to TDI in sensitized subjects, we performed a quantitative analysis of bronchial biopsies. Methods We obtained bronchial biopsies from six subjects with TDI asthrha 48 h after an asthmatic reaction induced by TDI challenge (challenged group), in six subjects with TDI asthma 1–4 weeks after the last exposure to TDI (chronic group), and in six non-asthmatic controls. The number of eosinophils, mast cells, T-lymphocytes, and IL-4 and IL-5 protein positive cells was determined by immunohistochemistry in the area 100 μn beneath the epithelial basement membrane. Results The characteristic increase of submucosal eosinophils, but not of mast cells and T-lymphocytes, was observed in the subjects with TDI-induced asthma when compared with controls. No differences were detected between the two groups of asthmatics. In the subjects with TDI-induced asthma, cell immunoreactivity for IL-5 was increased when compared with normal controls. There was no difference in the expression of IL-5 protein between challenged and chronic asthmatics. In contrast, the expression of IL-4 protein was increased only in the asthmatic subjects tested after recent exposure to TDI. Conclusions We demonstrated that TDI asthma 48 h after specific bronchial challenge was associated with increased numbers of cells expressing IL-4 and IL-5, whereas chronic TDI asthma was associated with increased expression of IL-5, but not of IL-4. The results suggest that subjects who developed TDI asthma exhibit increased production of IL-5 even in the absence of a recent trigger by the exogenous sensitizer and that production of TH₂-like cytokines in TDI-induced asthma may not always be co-ordinately regulated in vivo.