多器官功能障碍综合征血清炎性细胞因子变化的意义

目的 :探讨多器官功能障碍综合征 (MODS)血清炎性细胞因子的变化的意义。方法 :采用双抗体夹心酶联免疫吸附法测定 42例MODS和 3 0例健康对照组的血清肿瘤坏死因子 (TNF α)、白介素 1β(IL 1β)与白介素 6(IL 6)含量。结果 :MODS血清TNF α、IL 1β与IL 6含量 (各为2 77.64±5 4.3 6ng/L ,2 40 .97± 2 0 .87ng/L ,3 84.96± 73 .19ng/L)明显高于对照组 ( 2 3 .3 7± 7.96ng/L ,40 .65± 5 .87ng/L ,3 0 .2 6± 3 .61ng/L) ,P均 <0 .0 0 1;死亡组TNF α、IL 1β与IL 6含量 (各为5 5 4.86± 95 .69ng/L ,3 3 8.87± 41.2 1ng/L ,5 97.3 7± 118.3 6ng/L)高于非死亡组TNF α、IL 1β与IL 6含量 ( 2 77.64± 5 4.3 6ng/L ,2 40 .97± 2 0 .87ng/L ,3 84.96± 73 .19ng/L) ,P均 <0 .0 1。结论 :TNF α、IL 1β与IL 6对MODS的病理生理过程可能起作用 ,监测MODS患者血清TNF α、IL 1β与IL 6水平可作为反映病情严重程度和评估预后的一项参考指标     

慢性阻塞性肺疾病患者炎症细胞因子与肺通气功能的相关研究

目的　探讨慢性阻塞性肺疾病 (COPD)患者肺通气功能改变与炎症因子变化之间的关系。方法　稳定期COPD和慢性支气管炎 (简称慢支 )患者各 8例 ,,另有 8名健康者作为对照 ,进行肺功能检查 ,并经支气管肺泡灌洗获取肺泡巨噬细胞进行培养 ,采用酶联免疫吸附 (ELISA)方法测定大肠杆菌内毒素 (LPS)刺激后上清液中白细胞介素 8(IL 8)、IL 1β、IL 6和肿瘤坏死因子α(TNF α)的浓度 ,细胞因子之间相关性采用Pearson相关阵分析 ,肺功能值与细胞因子相关性采用多元后退回归法分析。结果　 (1)肺泡巨噬细胞释放IL 8:加入LPS后COPD组为 [(43± 2 7) μg/L和 (5 7± 41) μg/L],与正常对照组 [(13± 10 ) μg/L和 (2 0± 13 ) μg/L) ]比较差异有显著性 (P <0 .0 5 ) ;与慢支组 [(2 9± 2 1)μg/L和 (3 2± 2 3 ) μg/L]比较差异有显著性 (P >0 .0 5 )。 (2 )加入LPS前、后 ,COPD组、慢支组和正常对照组肺泡巨噬细胞释放IL 1β分别为 [(5 0± 41)ng/L、(94± 5 9)ng/L、(3 7± 3 2 )ng/L、(2 2 5± 10 8)ng/L、(15 3± 175 )ng/L、(70± 3 7)ng/L],与IL 8的释放呈正相关 (P <0 .0 5 ) ;三组肺泡巨噬细胞在LPS刺激后释放TNF α分别为 [(12 3 8± 679)ng/L、(3 0 88± 2 879)ng/L、(13 3 2± 1846)ng/L],与IL 1β呈正相     

鼠白细胞介素12质粒对小鼠支气管哮喘模型气道炎症及细胞因子的影响

目的　研究鼠白细胞介素 12 (IL 12 )基因表达 (mIL 12 )质粒对小鼠支气管哮喘 (简称哮喘 )模型气道炎症及细胞因子的影响 ,并分析其作用机制。方法　卵白蛋白 (OVA)致敏建立小鼠哮喘模型。BALB/c小鼠 4 1只 ,分为 6组。即哮喘模型组 (A组 ) 8只 :OVA致敏 +OVA气雾攻击 ;模型对照组 (B组 ) 6只 :用生理盐水代替 1%OVA溶液雾化 ,余处理同A组 ;mIL 12质粒预防组 (C组 ) 8只 :实验第 1、3、5天各肌肉注射mIL 12质粒 10 0 μg ;mIL 12质粒治疗组 (D组 ) 8只 :实验第 14、16、18天各肌肉注射mIL 12质粒 10 0 μg ;空质粒预防组 (E组 ) 5只 :实验第 1、3、5天各肌肉注射空质粒 10 0 μg ;空质粒治疗组 (F组 ) 6只 :实验第 14、16、18天各肌肉注射空质粒 10 0 μg。测定所有小鼠支气管 肺泡灌洗液 (BALF)中的嗜酸粒细胞 (EOS)个数和IL 4、IL 5、γ干扰素 (IFN γ)水平。结果B组小鼠EOS个数和IL 4、IL 5、IFN γ浓度分别为 (0 0 1± 0 0 3)× 10 8/L、(2 4± 4 ) pg/ml、(33± 6 ) pg/ml、(72 5± 5 9) pg/ml,C组为 (0 0 6± 0 0 4 )× 10 8/L、(43± 13) pg/ml、(6 3± 10 )pg/ml、(6 2 6± 6 0 ) pg/ml,D组为 (0 11± 0 12 )× 10 8/L、(38± 14 )pg/ml、(6 6± 14 ) pg/ml、(6 6 1± 4 0 ) pg/ml,与A     

肝硬化患者小肠细菌过度生长与内毒素血症

目的　研究肝硬化患者小肠细菌过度生长与血浆内毒素、白细胞介素 (IL) 2、IL 6及肿瘤坏死因子 (TNF) α水平的关系。方法　 71例肝硬化患者行葡萄糖 氢呼气试验 (GHBT)检测小肠细菌过度生长情况 ,鲎实验检测血浆内毒素水平及ELISA法检测血浆IL 2、IL 6及TNF α水平 ;分析血浆内毒素与血浆IL 2、IL 6及TNF α水平之间的关系。结果　 71例肝硬化患者中 ,GHBT阳性者为 1 8例(2 5 3 % )。肝硬化伴与不伴小肠细菌过度生长者血浆内毒素分别为 (0 71 5± 0 2 2 9)Eu/L、(0 379±0 2 2 3)Eu/L(P <0 0 0 1 ) ;IL 2分别为 (1 9 1 5± 4 60 )ng/L、(9 41± 6 69)ng/L ;IL 6分别为 (93 2 9± 2 7 37)ng/L、(53 2 2± 2 8 31 )ng/L ;TNF α分别为 (42 1 8± 1 6 91 )ng/L、(2 7 72± 1 7 0 6)ng/L(P值均 <0 0 1 )。肝硬化患者血浆内毒素与IL 2、IL 6及TNF α存在直线正相关 ,相关系数分别为 0 894、0 857、0 845(P值均 <0 0 0 1 )。结论　肝硬化伴小肠细菌过度生长患者血浆内毒素、IL 2、IL 6、TNF α水平均增高 ,提示肝硬化小肠细菌过度生长是导致肝硬化患者出现内毒素血症的原因之一。肝硬化患者血浆内毒素水平升高与血浆IL 2、IL 6、TNF α水平升高相关 ,提示肝硬化患者内毒素血症可刺激机体产生多     

肿瘤坏死因子α基因多态性与2型糖尿病胰岛素抵抗的相关性

目的　探讨肿瘤坏死因子α(TNF α)水平及其基因第 3 0 8位G→A变异与 2型糖尿病 (DM )胰岛素抵抗 (IR)的相关情况。方法　 ( 1)放射免疫法检测 70例 2型DM患者和 60例健康对照者空腹血清胰岛素 (FINS)、TNF α水平。 ( 2 )以PCR RFLP检测TNF α基因型。 ( 3 )用自我平衡模型分析法(HOMA)评价IR。结果　 ( 1) 2型DM组及对照组血清TNF α水平分别为 ( 1.2 6± 0 .2 8) μg/L和 ( 1.15±0 .2 4) μg/L(P <0 .0 5 ) ;FINS分别为 ( 11.3 1± 4.3 1)mIU/L和 ( 14 .67± 4.96)mIU /L(P <0 .0 1) ;HOMA IR分别为 5 .5 4± 2 .2 5和 3 .3 9± 1.48(P <0 .0 1)。 ( 2 ) 2型DM组和对照组GA +AA基因型频率分别为0 .3 0和 0 .13 ,A等位基因频率分别为 0 .16和 0 .0 7(P <0 .0 5 )。 ( 3 ) 2型DMGA +AA基因型组及GG基因型组TNF α分别为 ( 1.3 5± 0 .2 5 ) μg/L和 ( 1.2 2± 0 .16) μg/L(P <0 .0 5 ) ;FINS分别为 ( 13 .42± 4.73 )mIU /L和 ( 10 .40± 3 .63 )mIU/L(P <0 .0 1) ;HOMA IR分别为 7.42± 1.93和 4.11± 1.3 1(P <0 .0 1)。( 4 )多元逐步回归分析显示 :HOMA IR与TNF α及TNF α基因型呈显著正相关。结论　TNF α第 3 0 8位G→A变异与中国闽南人 2型DM的发生有关 ,A等位基因可能通过增加TNF α的释放     

急性呼吸窘迫综合征患者血浆白细胞介素4等含量变化的研究

目的　观察急性呼吸窘迫综合征 (ARDS)患者血浆白细胞介素 4(IL 4)、IL 10和IL 13含量的变化 ,探讨在ARDS发病机制中抗炎机制变化的意义。方法　采用酶联免疫吸附试验 (ELISA)方法 ,检测 2 2例ARDS患者 (ARDS组 )、8例全身炎症反应综合征 (SIRS)患者 (SIRS组 )和 10名健康志愿者 (正常对照组 )的动脉血血浆IL 4、IL 10和IL 13的含量。结果　ARDS组患者的血浆IL 4、IL 10和IL 13含量分别为 (2 61± 5 5 ) μg/L、(45 8± 112 ) μg/L、(5 2 1± 2 0 2 ) μg/L ,SIRS组分别为 (15 5± 2 6)μg/L、(2 60± 5 4) μg/L、(1 69± 0 3 9) μg/L ,正常对照组分别为 (43± 13 ) μg/L、(13 5± 15 ) μg/L、(0 3 3±0 10 ) μg/L ,三组间比较差异具有非常显著性 (P均 <0 0 1) ;SIRS组与正常对照组比较 ,差异也有显著性 (P <0 0 1)。结论　抗炎性细胞因子IL 4、IL 10和IL 13的释放异常 ,可能是ARDS和SIRS的重要发病机制之一。     

Toll样受体4与大鼠肺泡巨噬细胞内毒素耐受性的实验研究

目的　观察大鼠肺泡巨噬细胞对内毒素 (LPS)重复刺激的耐受性与其Toll样受体 4(TLR4)表达的变化 ,研究两者之间的联系。方法　将 30只Wistar雄性大鼠分离所得肺泡巨噬细胞 ,用随机数字表法分为正常对照组 (A组 ) ,LPS单次刺激组 (B组 )和LPS 2次重复刺激组 (C组 )。用酶联免疫吸附测定 (ELISA)法和逆转录 聚合酶链反应 (RT PCR)法分别检测各组大鼠肺泡巨噬细胞分泌肿瘤坏死因子α(TNF α)及TLR4、白细胞介素 1 0 (IL 1 0 )、IL 1 8mRNA表达的变化 ,WesternBlot检测TLR4蛋白表达的变化。结果　大鼠肺泡巨噬细胞TNF α分泌和TLR4、IL 1 0、IL 1 8mRNA表达及TLR4的蛋白表达水平 ,A组分别为 (0 4 5 0± 0 0 1 0 ) μg/L、1 1 6± 0 0 4、0 97± 0 0 3、1 32 0± 0 0 2 0、5 8 1± 0 4 ;B组分别为 (0 76 0± 0 0 30 ) μg/L、2 1 8± 0 0 9、1 83± 0 0 7、2 0 6 0± 0 0 6 0、1 4 8.3± 1 4 ;B组与A组比较差异有显著性 (P <0 0 1 ) ;C组分别为 (0 4 90± 0 0 5 0 ) μg/L、1 2 3± 0 0 3、1 1 5± 0 0 5、1 1 70± 0 0 4 0、96 5±0 7;C组与B组比较差异也有显著性 (P <0 0 5或 <0 0 1 )。结论　LPS重复刺激可使大鼠肺泡巨噬细胞对LPS产生耐受性 ;LPS耐受性的产生与TLR4表达     

老年充血性心力衰竭患者胰岛素抵抗与肿瘤坏死因子-α的相关分析

目的　研究老年充血性心力衰竭 (心衰 )患者胰岛素抵抗 (IR)与肿瘤坏死因子 α(TNF α)的相关关系及临床意义。　方法　采用放射免疫分析法测定 5 2例老年充血性心力衰竭患者、36例老年健康志愿者和 30例非老年健康志愿者空腹胰岛素、TNF α ,选择空腹胰岛素与血糖乘积的倒数(IAI)作为评价老年人心衰状态下的胰岛素敏感性指数 ,对IAI、左室射血分数 (LVEF)、心功能分级及TNF α进行相关分析。　结果　老年心衰组的IAI低于老年健康组 (- 1 75± 0 17对 - 1 36± 0 16 ,P <0 0 5 ) ,并随着心功能的恶化而进一步降低 (- 1 87± 0 16对 - 1 6 8± 0 15 ,P <0 0 5 ) ;但不同病因组IAI差异无显著性 (F =2 0 2 ,P >0 0 5 )。老年心衰组的空腹胰岛素和TNF α均显著高于老年健康组〔(18 2 9± 6 80 )对 (8 78± 3 35 )mIU/L)和 (0 36± 0 13)对 (0 2 1± 0 12 ) μg/L ,P <0 0 5〕 ,且心衰程度越重 ,空腹胰岛素和TNF α的水平越高〔(2 2 46± 9 12 )对 (16 41± 5 0 6 )mIU/L和 (0 41± 0 17)对 (0 31± 0 15 ) μg/L ,P <0 0 5〕。老年心衰患者TNF α与IAI呈显著负相关 (r=- 0 76 ,P <0 0 5 )。　 结论　老年心衰患者的IAI和TNF α存在着相关性 ,IAI和TNF α水平可作为评价心衰严重程度     

肌钙蛋白与肿瘤坏死因子α在病毒性心肌炎急性期检测的临床意义

目的 :探讨心肌损伤指标肌钙蛋白T(cTnT)与非特异细胞炎症因子肿瘤坏死因子 α(TNF α)在急性病毒性心肌炎 (VMC)患者中检测的临床意义。 方法 :实验组为 36例诊断为急性VMC患者 ,检测 36例VMC患者发病 1周内血清cTnT及TNF α ,并与对照组 4 0例的检测结果进行比较。 结果 :cTnT平均值 :VMC组为 (0 .6 0 2 5± 0 .5 36 9) μg/L ,对照组为 (0 .0 12 1±0 .0 0 0 2 ) μg/L ,两组比较差异有非常显著性意义 (P <0 .0 1) ;TNF α平均值 :VMC组为 (45 .12± 2 9.0 1)ng/L ,对照组为 (3.2 4± 3.17)ng/L ,两组比较差异有非常显著性意义 (P <0 .0 1)。 结论 :与对照组比较 ,VMC患者在急性期中 ,cTnT及TNF α均有明显升高 ,而且二者密切相关 ,说明TNF α在心肌损伤过程中起着重要作用。     

不卧床持续性腹膜透析患者血浆和透析排出液中细胞因子的变化及意义

目的 :研究不卧床持续性腹膜透析 (CAPD)患者血浆和腹膜透析排出液中细胞因子的水平与腹膜透析和机体防御功能的关系。　 方法 :用酶免疫法测定 2 1例非感染期CAPD患者血浆和腹膜透析排出液中IL 1α、IL 1β、IL 6、TNFα、IFNγ和可溶性肿瘤坏死因子受体 1(sTNFR1)水平 ,同时做 4h腹膜平衡试验。比较细胞因子水平与腹透情况和腹膜转运特性的关系 ;另外 ,与同期测定的正常人血浆IL 6和sTNFR1水平作对比研究。　 结果 :2 1例CAPD患者血浆和腹透液中各种细胞因子水平分别为 :IL 1α 34 40± 12 87ng/L和 17 6 0± 10 49ng/L(P <0 0 0 1) ;IL 6 8 10± 14 6 9ng/L和 15 7 6 5± 130 2 3ng/L(P <0 0 0 1) ;TNFα 117 30± 195 2 7ng/L和 2 2 90± 13 37ng/L(P <0 0 5 ) ;sTNFR19 76± 0 98μg/L和 1 84± 2 72 μg/L(P <0 0 0 1)。仅在 8例患者血浆及 9例患者腹透液中检测出IL 1β;在 1例患者血浆中测到IFNγ ,腹透液中IFNγ为 2 14± 0 74kU/L。腹透液中IL 6和IFNγ水平呈负相关 (P <0 0 2 )。血浆和腹透液中各种细胞因子水平与腹透时间长短、既往感染与否、透析充分性和超滤量以及腹膜转运特性均无关系。CAPD患者血浆IL 6和sTNFR1水平比正常人明显升高 (P <0 0 0 1)。　 结论 :腹透液中IL     

哮喘患者痰液细胞因子和哮嗜酸细胞阳离子蛋白水平及意义

目的 探讨痰中细胞因子、嗜酸细胞阳离子蛋白（ＥＣＰ）水平与哮喘严重程度的关系。方法 采用酶联免疫法及荧光光免疫法对轻（Ｍ组１０例）中、重度（ＭＳ组１５例）哮喘２痰液白细胞介素（ＩＬ）５、肿瘤坏死因子α（ＴＮＦ－α）、可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）、ＥＣＰ水平进行检测。结果 中、重度哮喘患溶液ＩＬ－５（３５ｎｇ／Ｌ以上）、ＴＮＦ－α（Ｍ组为１４９±５９ｎｇ／Ｌ，ＭＳ组为２６７±１４７ｇ／Ｌ     

Airway inflammation and basement membrane tenascin in newly diagnosed atopic and nonatopic asthma

Previous studies have shown both similar and distinct inflammatory changes in atopic and nonatopic asthma. This study was set to investigate the bronchial inflammatory cell infiltrate and subepithelial basement membrane (BM) tenascin deposition in subjects with newly diagnosed asthma and bronchial hyperresponsiveness (BHR). Seventy-nine asthmatic subjects (age 18-60 years) were recruited and 58 were atopic according to skin prick testing. The patients recorded asthma symptoms and peak flow measurements for 14 days. Lung function and BHR were measured by spirometry and histamine challenge. Serum eosinophil cationic protein (ECP) and blood eosinophils were assessed. Fiberoptic bronchoscopy was performed to obtain bronchial biopsies. Serum ECP was higher in the atopic group but eosinophil counts did not differ. There were no differences in inflammatory cells studied (activated eosinophils, T-lymphocytes, mast cells or macrophages) between nonatopic and atopic subjects. BM tenascin layer was significantly thicker in atopic compared with nonatopic subjects (7.6 vs 6.3 microm, P = 0.007). The thickness of tenascin correlated with eosinophil, T-lymphocyte, and macrophage counts, as well as with IL-4-positive cell counts and the correlation was seen only in atopic asthmatics. These findings suggest that inflammatory cells may have a regulatory role in tenascin expression in atopic asthma.     

Relationship between the tumor necrosis factor system and the serum interleukin-4, interleukin-5, interleukin-8, eosinophil cationic protein, and immunoglobulin E levels in the bronchial hyperreactivity of adults and their children.

The aim of the study was to investigate the activation of inflammatory mediators interleukin (IL)-4, IL-5, and IL-8; immunoglobulin E (IgE); and eosinophil cationic protein (ECP) and to evaluate the regulatory role of the tumor necrosis system (TNF) system in bronchial hyperreactivity. Adults who had suffered from bronchial asthma in childhood but who had been symptom free for at least 3 years were examined together with their children who did not have asthma. The serum concentrations of TNF-alpha, soluble TNF receptor 1 (sTNF-R1), TNF-R2, IL-4, IL-5, IL-8, ECP, and IgE were studied in symptom-free adults (n = 22) and their children (n = 22) with bronchial hyperreactivity. Nonhyperreactive individuals with a similar medical history (adults, n = 17; children, n = 20) served as controls. Significantly elevated serum TNF-alpha (X +/- SD: 5.13 +/- 1.37 pg/mL versus 3.91 +/- 0.61 pg/mL; p < 0.0001), sTNF-R1 (X +/- SD: 1.37 +/- 0.28 ng/mL versus 1.16 +/- 0.13 ng/mL; p = 0.0002), and sTNF-R2 (X +/- SD: 0.78 +/- 0.42 ng/mL versus 0.43 +/- 0.41 ng/mL; p = 0.0001); IL-4 (X +/- SD: 4.05 +/- 1.02 pg/mL versus 3.34 +/- 0.84 pg/mL; p = 0.0016); IgE (X +/- SD: 390.1 +/- 361.4 KU/L versus 130.2 +/- 166.1 KU/L; p = 0.0001); and ECP (X +/- SD: 17.57 +/- 11.03 micrograms/L versus 10.65 +/- 6.01 micrograms/L; p = 0.0016) concentrations were measured in the subjects with bronchial hyperreactivity as compared with the nonhyperreactive group. Significant positive linear correlations were observed for the bronchial hyperreactive group between the concentrations of TNF-alpha and ECP, TNF-alpha and sTNF-R1, TNF-alpha and IL-8, sTNF-R1 and ECP, sTNF-R1 and IL-8, and sTNF-R2 and IL-8. Moreover, the TNF-alpha and sTNF-R2 levels correlated with the airway reactivity in the hyperreactive group. We suggest that the elevated cytokine levels indicate activation of the immune system in individuals who were previously asthmatic, but recovered, and are now symptom free and in their children with nonasthmatic bronchial hyperreactivity. The TNF system may play a key role in the pathomechanism of bronchial hyperreactivity.     

哮喘和慢性阻塞性肺疾病患者糖皮质激素治疗前后痰液炎性标志物 …

探讨哮喘和慢性阻塞性疾病患者吸入糖皮质激素治疗后痰液中细菌因子和嗜酸细胞阳离子蛋白浓度及糖皮质激素对其影响。方法采用荧光酶联免疫法检测糖皮质激素治疗前后痰液中白细胞介素（ＩＬ）－５、ＩＬ－８、ＥＣＰ浓度及嗜酸细胞和嗜中性粒细胞计数。     

呼吸道合胞病毒感染对哮喘患儿单个核细胞表达白细胞介 …

目的 观察呼吸道合胞病毒（ＲＳＶ）感染对哮喘患儿螨诱导单个核细胞（ＰＢＭＣ）表达白细胞介素４（ＩＬ－４）和ＩＬ－５的影响及其与哮喘的关系。方法 用 联免疫吸附试验（ＥＬＩＳＡ）及逆转录（ＲＴ）－聚合酶链反应（ＰＣＲ）法 ３０例螨过敏哮喘患儿「其中ＲＳＶ感染者１６例（Ａ组），无ＲＳＶ感染者１４例（Ｂ组）」和１０名年龄组正常对照组（Ｃ组）的外周血ＰＢＭＣ经螨诱导表达ＩＬ－４及ＩＬ－５的水平，并分析其与     

Apoptotic eosinophils in sputum from asthmatic patients correlate negatively with levels of IL-5 and eotaxin

BACKGROUND: Eosinophilic inflammation of the airways is a key characteristic of asthma. A defect in eosinophil apoptosis might contribute to the chronic tissue eosinophilia associated with asthma. OBJECTIVE: Our purpose was to examine whether the occurrence of apoptotic eosinophils in induced sputum from asthmatic patients correlate with interleukin (IL)-5 and eotaxin. METHODS: Thirty stable and 30 exacerbated asthmatic patients were recruited. Twenty healthy subjects were enrolled as a control group. Induced sputum was obtained from asthmatic patients and from control subjects. The number of apoptotic eosinophils in sputum was assessed by flow cytometry. In sputum supernatant, eosinophil cationic protein (ECP) was measured by sensitive radioimmunoassay, and IL-5 and eotaxin by sandwich enzyme linked immunosorbant assay. RESULTS: Levels of eosinophils, apoptotic eosinophils, IL-5, ECP and eotaxin from asthmatic patients were higher than those from healthy subjects. Thirty exacerbated asthmatics showed higher proportions of eosinophils (median 29.3%, range 13.4%-40.9%), more detectable levels of IL-5 (50.44, 32.99-67.01 pg/ml) and eotaxin (644.6, 197.4-937.7 pg/ml) in their sputum than the patients with stable asthma (P<0.05). There were significant inverse correlations between the levels of sputum IL-5 and the proportion of sputum eosinophil apoptosis in patients with exacerbated and stable asthma (r=-0.85 and -0.79, P<0.01 and P<0.05, respectively). Also inverse correlations were found between the levels of eotaxin and the proportion of sputum eosinophil apoptosis in exacerbated (r=-0.85, P<0.01), or stable asthma (r=-0.69, P<0.05). Additional positive correlations between the levels of sputum IL-5 and eotaxin in either exacerbatated (r=0.93, P<0.01) or stable asthma (r=0.82, P<0.05) were observed. CONCLUSIONS: Apoptosis of eosinophils might be suppressed by proinflammatory cytokines and chemokines such as IL-5 and eotaxin leading to their accumulation in the lung. Stimulation of eosinophils in airway with IL-5 and eotaxin may play a crucial role in allergic inflammation.     

吸入糖皮质激素对哮喘患者诱导痰炎性细胞蛋白激酶Cα表达及白细胞介素-5的影响

目的　观察哮喘患者气道炎性细胞中蛋白激酶C(PKCα)的表达和白细胞介素 (IL) 5的水平 ,及吸入糖皮质激素 (以下简称激素 )对其的影响。方法　 2 9例哮喘患者分为激素治疗 2周组 ( 14例 )和激素治疗 4周组 ( 15例 ) ,治疗前后行诱导痰和肺功能检查。免疫组化 (SP法 )测PKCα在诱导痰炎性细胞中的表达 ,ELISA测诱导痰上清中IL 5的含量。结果　哮喘患者治疗前诱导痰中嗜酸性粒细胞 (EOS)与淋巴细胞相对计数、炎性细胞中PKCα阳性表达率与IL 5含量均高于健康对照组 (P <0 0 1) ,治疗后均明显下降 (P <0 0 1) ,但仍高于健康对照组 (P <0 0 1) ,激素治疗 2周组与激素治疗 4周组间无明显差异 (P >0 0 5 )。第 1秒钟用力呼气容积 (FEV1)占预计值的百分比与炎性细胞中PKCα的阳性表达率、IL 5浓度、EOS相对计数呈负相关 (r =- 0 4 2 3,P <0 0 5 ;r =- 0 6 6 4 ,P <0 0 1;r =-0 5 78,P <0 0 1) ;IL 5浓度与炎性细胞中PKCα的阳性表达率、EOS相对计数呈正相关 (r =0 6 2 3,P<0 0 1;r=0 75 8,P <0 0 1)。结论　PKCα信号途径可能为哮喘气道炎症发生的重要机制之一 ;吸入激素可明显降低气道IL 5的含量和炎性细胞PKCα阳性表达率 ,但短期内不能使气道炎症完全恢复正常     

重度支气管哮喘患者气道炎症及其与白细胞介素17的关系

目的探讨重度支气管哮喘(简称哮喘)患者气道炎症特征及其可能机制,并进一步观察吸入糖皮质激素治疗对气道炎性细胞分类计数、炎症介质、白细胞介素17(IL-17)和IL-8等细胞因子的影响。方法分别选择轻度(轻度组)、中度(中度组)和重度(重度组)持续哮喘患者16例、14例和18例,正常对照组15名,采用基线评估包括哮喘症状控制评分、肺功能测定和用诱导痰检查方法对痰炎性细胞进行分类计数;采用酶联免疫吸附测定(ELISA)法检测痰IL-17和IL-8浓度;采用酶联免疫荧光法测定嗜酸粒细胞阳离子蛋白(ECP)浓度;采用比色法测定中性粒细胞髓过氧化物酶(MPO)浓度,并用痰液蛋白含量进行校正。然后规范吸入糖皮质激素治疗4周,随访轻、中度和重度哮喘患者各15例复查上述指标。结果痰嗜酸粒细胞(EOS)比值和ECP浓度在每克蛋白中轻度组分别为0.0670±0.0740、(155±91)×10-6g;中度组分别为0.0830±0.0440、(180±83)×10-6g;重度组分别为0.1240±0.1430、(191±87)×10-6g,与正常对照组[0.0000±0.0010、(44±25)×10-6g]比较差异有统计学意义(P<0.01);但各哮喘组间比较差异无统计学意义(P>0.05)。中性粒细胞比值在重度组为0.589±0.203,与轻度组(0.455±0.154)、中度组(0.449±0.194)、正常对照组(0.313±0.134)比较差异有统计学意义(P<0.01)。MPO水平在每克蛋白中,重度组为(31±10)U,轻度组为(12±4)U、中度组为(22±7)U,与正常对照组[(10±4)U]比较差异有统计学意义(P<0.01)。IL-17水平在每克蛋白中重度组为(264±137)×10-9g,中度组为(172±65)×10-9g,轻度组为(126±52)×10-9g,与正常对照组[(56±20)×10-9g]比较差异有统计学意义(P<0.01);IL-8浓度在每克蛋白中,重度组为(531±321)×10-9g,轻度组为(410±181)×10-9g,中度组为(438±148)×10-9g,正常对照组为(83±36)×10-9g,重度组与正常对照组比较差异有统计学意义(P<0.01);而轻度组与中度组间比较差异无统计学意义(P>0.05)。IL-17水平与IL-8、中性粒细胞与MPO呈显著相关(r分别为0.525、0.349、0.602,P均<0.01)。经糖皮质激素治疗后,对轻、中、重度30例哮喘患者进行合并分析表明,EOS、ECP、MPO、IL-17和IL-8均显著降低;但两组患者的中性粒细胞比值在治疗后比较差异均无统计学意义(P>0.05);但重度组(0.642±0.157)与轻、中度哮喘组(0.394±0.147)比较差异有统计学意义(P<0.01)。结论中性粒细胞增多是重度哮喘的气道炎症特征之一,IL-17/IL-8可能参与中性粒细胞向气道内的募集。     

Relationship between the perception of dyspnoea and airway inflammatory markers

Poor dyspnoea perception in asthmatic patients seems to be associated with increased risk of asthma exacerbation. We have studied the relationship between basel ne dyspnoea perception and inflammatory markers in sputum in eight patients with mild asthma and in 13 patients with moderate to severe asthma.The perception of dyspnoea was scored on the Borg scale. Eosinophilic cationic protein (ECP) was measured by fluoroimmunoassay and by an interleukin (IL)-5 sandwich ELISA. The baseline Borg score was significantly higher in patients with severe asthma than in patients with mild to moderate asthma (4.1 +/- 0.29 vs. 2.28 +/- 0.28, P<0.05).The proportion of eosinophil and ECP levels in the sputum were significantly higher in patients with moderate to severe asthma. IL-5 in sputum was significantly increased in moderate to severe asthmatic patients compared to mild asthmatic patients. A significant relationship was found between the baseline perception score and FEV1/FVC (r = -0.53, P<0.01), sputum eosinophils (r = 0.70, P<0.01) and sputum ECP (r = 0.62, P<0.01).These findings suggest that the baseline perception score is related to inflammatory markers in sputum, and that the perception of dyspnoea as well as airway inflammatory markers may be considered to evaluate asthma severity.     

Reproducibility of measurements of exhaled NO, and cell count and cytokine concentrations in induced sputum.

Sputum induction is a noninvasive, well-tolerated method for studying airway inflammation. When induction with hypertonic saline is repeated at short time-intervals (<24 h), the cell profile of sputum has not been reproducible. To determine the proper interval between sampling cell profiles and cytokine contents of sputum samples that had been induced 48 h apart, were compared. In addition, the inducible nitric oxide synthase (iNOS) expression of sputum cells was compared to the levels of exhaled nitric oxide (NO). Sputum induction and measurement of exhaled NO was performed in 31 healthy nonatopic volunteers. Cell differentials were counted. Concentrations of interleukin (IL)-4, IL-6, tumour necrosis factor (TNF)alpha, eosinophil cationic protein (ECP) were measured in sputum supernatant, and iNOS was determined. Reproducibility of cell counts was high (r=0.836 total cells, r=0.762 neutrophils, r=0.966 eosinophils, r=0.742 macrophages). IL-4 (r=0.398), IL-6 (r=0.566), TNFalpha (r=0.658) and ECP (r=0.501) were also less reproducible in healthy volunteers. Consistent with the low levels of NO in the exhaled air (18.5+/-2.6 ppb and 19.3+/-2.8 parts per billion (ppb) on the two study days, r=0.976, p=0.0000), expression of iNOS was not detected. In conclusion, in healthy subjects, induced sputum cell counts are reproducible. Even though the success rate in nonatopic populations is relatively low, sputum induction appears to be a valid method for detecting inflammatory changes within the airways, when being performed 48 h apart.