变应性鼻炎患者脱敏治疗前后白细胞介素-18水平变化

目的:探讨白细胞介素18(IL18)在变应性鼻炎(AR)的发病过程中的作用及脱敏治疗的作用机制。方法:以健康者作对照(对照组),用酶联免疫吸附方法检测AR患者(AR组)脱敏治疗(1年)前、后血清IL18水平。结果:AR组脱敏治疗前血清IL18水平(88.33±35.95)ng/L低于对照组(149±47.37)ng/L,2组比较差异有统计学意义(P<0.05)。而AR组脱敏治疗后血清IL18水平(199.22±58.82)ng/L明显升高,与对照组比较差异无统计学意义(P>0.05)。结论:IL18在AR组中低表达,而在脱敏治疗后表达增高,提示IL18在变应性炎症的发生、发展和脱敏治疗中起了重要作用。     

重组激活基因-1在变应性鼻炎鼻黏膜中的表达及DNA测序研究

目的:探讨重组激活基因1(RAG1)在变应性鼻炎(AR)发病机制中的作用及其与IL4、IL10和IgE之间的关系及意义。方法:用卵清蛋白(OV)建立大鼠AR模型并用地塞米松(DEX)进行干预,用被动皮肤过敏原试验(PCA)测试皮肤反应并与正常对照组进行比较;用RTPCR技术检测各组鼻黏膜中RAG1基因mRNA的表达水平,并对RAG1基因的DNA进行测序;用ELISA法检测各组大鼠外周血清IL4、IL10和IgE的水平变化。结果:RAG1基因的mRNA在正常对照组鼻黏膜中未见表达,在AR组和DEX干预组均有明显表达;DNA测序未发现RAG1基因有突变发生;AR组血清IL4[(106.31±12.90)ng/L]和IgE[(38.67±4.13)ng/L]水平均显著高于正常对照组[(93.65±7.78)ng/L,(23.27±1.36)ng/L](均P<0.05),IL10[(38.15±4.89)ng/L]水平显著低于正常对照组[(48.74±3.49)ng/L](P<0.05);经DEX干预后,血清IL4[(92.67±16.40)ng/L]和IgE[(24.23±4.38)ng/L]水平均较AR组显著下降(均P<0.05),而IL10[(46.18±5.01)ng/L]水平较AR组显著升高(P<0.05);PCA试验在AR组90%呈阳性反应,在正常对照组和DEX干预组均呈阴性反应。结论:RAG1的高表达与AR的发病密切相关,并介导了IL4和IgE的分泌及抑制IL10的分泌。其DNA序列在AR鼻黏膜中具有保守性,糖皮质激素不影响RAG1基因的表达,推测在AR发病机制中,RAG1基因通过一个较高层面的免疫调节环节发生作用。     

鼻用皮质类固醇对鼻息肉中白细胞介素5mRNA表达的影响

目的　探讨短期 (6～ 8周 )应用鼻用皮质类固醇治疗对鼻息肉组织中白细胞介素 5(interleukin 5 ,IL 5 )mRNA表达的影响。方法　采用合成地高辛标记的互补RNA探针进行原位杂交 ,观察经鼻用皮质类固醇———布地奈德治疗 6～ 8周和未经治疗的鼻息肉组织 (各 2 0例 )中 ,IL 5mRNA阳性细胞浸润的变化情况。结果　①鼻息肉组织中IL 5mRNA阳性细胞主要为淋巴细胞和嗜酸粒细胞 ,且变应性 [(12 6± 4 6 ) / 0 2 5mm2 ]和非变应性患者 [(14 3± 4 1) / 0 2 5mm2 ]IL 5mRNA阳性细胞的密度差异无显著性 (t=- 0 775 ,P >0 0 5 ) ;②经鼻用皮质类固醇治疗的鼻息肉组织 [(10 2± 3 1) / 0 2 5mm2 ]的IL 5mRNA阳性细胞密度明显低于对照观察的鼻息肉组织 [(13 9±4 2 ) / 0 2 5mm2 ](t=3 114 ,P <0 0 1)。结论　短期 (6～ 8周 )应用鼻用皮质类固醇治疗可抑制鼻息肉组织中IL 5mRNA的表达水平。     

变应性鼻炎患者外周血嗜酸粒细胞-骨髓干细胞通路指标检测在激素治疗评价中的意义

目的 检测健康人及变应性鼻炎(AR)患者治疗前后外周血嗜酸粒细胞(eosinophils,EOS)-骨髓干细胞通路相关指标CD34+、白细胞介素5(IL-5)、EOS,探讨外周血-骨髓通路在变应性鼻炎发病机制中的作用以及糖皮质激素对此通路的影响.方法 实验分2组:①试验组:常年性持续性变应性鼻炎患者44例,男24例,女20例,年龄7～68岁;给予糖皮质激素治疗4周;②健康对照组:健康体检者30例.分别检测试验组治疗前后和对照组外周血EOS计数,血清IL-5水平及CD34+细胞数,并分析各指标间的相关性.结果 试验组治疗前血清IL-5含量、CD34+数分别为(88.25±33.47)ng/L、(9.24±2.15)个/105,显著高于治疗后[(44.34±16.32)ng/L、(6.31±1.83)个/103]及健康对照组[(31.24±8.43)ng/L、(3.47±1.32)个/105].试验组治疗前后血清IL-5水平与其CD34+数呈显著正相关(r值分别为0.64、0.61,P值均＜0.01).患者血清IL-5水平与其EOS数呈显著正相关(r=0.64,P＜0.01).结论 外周血EOS、IL-5及CD34+细胞参与AR发病过程,提示AR患者病变局部组织和骨髓造血之间有相关通路存在.通过检测外周血IL-5及CD34+可评价治疗效果.     

白细胞介素-12在变应性鼻炎鼻粘膜中的表达

目的 :探讨白细胞介素 12 (IL 12 )在变应性鼻炎鼻粘膜中的表达。方法 :以卵清蛋白为变应原建立豚鼠变应性鼻炎模型 (模型组 )。取该模型和健康豚鼠鼻粘膜行常规HE染色 (对照组 ) ,并采用逆转录 聚合酶链反应 (RT PCR)检测方法 ,对两组动物鼻粘膜组织中IL 12mRNA表达水平进行相对定量比较。结果 :IL 12mR NA在两组鼻粘膜中均有表达 ,模型组的表达水平为 0 .6 6 7± 0 .10 4显著低于正常对照组 0 .84 7± 0 .0 71(P <0 .0 1)。结论 :在变应性鼻炎鼻粘膜组织中IL 12的表达下降 ,提示应用IL 12替代疗法治疗变应性鼻炎的可能性。     

芦荟治疗大鼠实验性变应性鼻炎的分子生物学研究

目的 :探讨芦荟 (aloevera)治疗大鼠实验性变应性鼻炎的作用机制。方法 :用卵清蛋白致敏大鼠制成变应性鼻炎动物模型 ,将芦荟经鼻给药 ,观察其行为学差异 ;用组织病理学方法观察鼻粘膜改变 ;用逆转录 多聚酶链反应 (RT PCR)对鼻粘膜和脾组织IL 2 ,IL 4mRNA进行定量检测。结果 :行为学得分 ,阳性对照组[(8.4 2± 1.0 6 )分 ]明显高于实验组 [(2 .0 2± 0 .4 2 )分 ]和正常对照组 (0分 ) ,其差异有极显著性意义 (P <0 .0 1) ;实验组鼻粘膜炎性反应明显轻于阳性对照组 ;实验组IL 2mRNA表达水平明显高于阳性对照组 ,其差异有极显著性意义 (P <0 .0 1) ;实验组IL 4mRNA表达水平明显低于阳性对照组 ,其差异也有极显著性意义 (P <0 .0 1)。结论 :芦荟通过改变TH1和TH2细胞因子基因表达 ,调节CD4+ 淋巴细胞亚群分化而发挥治疗变应性鼻炎的作用     

变应性鼻炎与气道高反应的关系

目的 :探讨变应性鼻炎与气道高反应性的相关性。方法 :用 1∶ 1 0 0 ( w/v)蒿属花粉对 50例变应性鼻炎和 2 0例正常者做支气管激发试验 ,分别测定两组第 1秒用力呼气量 ( FEV1) ;测血清中嗜酸性粒细胞阳离子蛋白 ( ECP)。结果 :支气管激发试验前 ,两组支气管均无症状 ,鼻炎组FEV1为 ( 70± 2 0 ) % ,对照组为 ( 85.6± 8.9) % ,两组有显著性差异 ( P <0 .0 1 ) ;支气管激发后 ,鼻炎组中 2 3例胸部有紧迫感 ,1 0例有哮鸣 ,5例有喘息 ,1 2例无症状 ,激发阳性率为 76%。对照组均无支气管症状。激发后鼻炎组 FEV1为 ( 60± 2 0 ) % ,对照组为 ( 85.6± 8.9) % ,两组有显著性差异 ( P <0 .0 5)。鼻炎组 ECP为 ( 30 .37± 1 8.92 ) μg/L,对照组为 ( 5.2 4± 3.2 3) μg/L,两组有显著性差异 ( P <0 .0 5)。结论 :变应性鼻炎不仅鼻粘膜有变态反应所致的慢性炎症 ,而且大部分气道也有慢性炎症反应而导致气道高反应性。     

血清IL-4、IFN-γ与持续性变应性鼻炎的相关性

目的探讨T辅助细胞亚群失衡介导的免疫反应在常年性变应性鼻炎中的作用。方法24例常年性变应性鼻炎患者和17例健康志愿者,应用酶联免疫试剂盒检测血清白细胞介素-4(IL-4)、γ-干扰素(IFN-γ)水平并进行比较分析。结果常年性变应性鼻炎组血清IL-4含量[37．8±18．36]pg/L明显高于对照组[1．74±3．35] pg/L；IFN-γ含量[0．72±3．35]pg/L明显低于对照组[43．60±22．87]pg/L,其差异有显著性意义(P＜0．01)。常年性变应性鼻炎组血清IFN-γ/IL-4比值明显下调。结论T辅助细胞亚群比例失衡,Th2功能亢进是常年性变应性鼻炎发病的重要原因。     

树突状细胞在变应性鼻炎实验小鼠发病机制中作用的研究

目的:探讨树突状细胞(DC)在变应性鼻炎实验小鼠发病中的可能作用及机制。方法:采用CpGoligodeoxynucleotide(CpGODN1826)培养诱导变应性鼻炎实验小鼠静脉血DC,进而检测DC协同刺激分子CD80、CD86的表达,以及其分泌的IL10、IL12等水平的变化。结果:实验小鼠静脉血DC其分泌IL10水平(3.6±0.5)μg/L明显低于对照组(6.8±0.8)μg/L,差异有统计学意义(t=20.608,P<0.01);分泌IL12水平(29.5±6.4)ng/L也明显低于对照组(46.2±9.8)ng/L,差异有统计学意义(t=5.979,P<0.01);同时,实验小鼠静脉血人类白细胞抗原DR(20.2±1.3)和协同刺激分子CD86的表达水平(36.8±13.5)明显高于对照组(11.6±1.5)和(26.7±8.5),差异有统计学意义(t=23.301和3.314,均P<0.01)。结论:DC可能通过诱导Th1/Th2细胞分化在变应性鼻炎实验小鼠发作时起重要作用,其可能的机制系通过DC分泌的细胞因子而起作用。     

细胞间黏附分子-1和白细胞介素-6在变应性鼻炎鼻和支气管黏膜中的表达及意义

目的 :探讨细胞间黏附分子 1(ICAM 1)、白细胞介素 6 (IL 6 )在变应性鼻炎鼻及支气管黏膜中的表达及意义。方法 :采用免疫组织化学方法检测ICAM 1、IL 6在 2 8例变应性鼻炎患者 (鼻炎组 )及 12例健康志愿者 (对照组 )的鼻、支气管黏膜中的表达。结果 :ICAM 1在鼻炎组鼻和支气管黏膜中的表达率分别为 10 0 .0 0 %和92 .86 % ,其差异无统计学意义 (P >0 .0 5 ) ;对照组鼻、支气管黏膜中ICAM 1表达率 (分别为 6 6 .6 7%和 5 8.33% )分别与鼻炎组 (分别为 10 0 .0 0 %和 92 .86 % )比较 ,差异均有统计学意义 (分别P <0 .0 1和P <0 .0 5 )。IL 6在鼻炎组鼻、支气管黏膜中的表达率分别为 10 0 .0 0 %、82 .14 % ,其差异无统计学意义 (P >0 .0 5 ) ;对照组鼻、支气管黏膜中IL 6表达率均为 4 1.6 7% ,分别与鼻炎组 (分别为 10 0 .0 0 %和 82 .14 % )比较 ,差异均有统计学意义 (分别P<0 .0 1和P <0 .0 5 )。结论 :ICAM 1、IL 6是呼吸道变态反应性炎症中的重要细胞因子 ,上、下呼吸道变应性炎症密切相关 ;同时治疗上、下呼吸道炎症性疾病 ,才能取得更好的治疗效果。     

Nasal interleukin-5, immunoglobulin E, eosinophilic cationic protein, and soluble intercellular adhesion molecule-1 in chronic sinusitis, allergic rhinitis, and nasal polyposis

OBJECTIVE: To compare concentrations of interleukin-5 (IL-5), immunoglobulin E (IgE), eosinophilic cationic protein (ECP), and soluble intercellular adhesion molecule-1 (sICAM-1) in nasal secretion and serum of patients with chronic nonallergic sinusitis, allergic rhinitis, and nonallergic nasal polyposis to obtain information about the pathogenesis of these diseases. METHODS: Nasal secretion and serum were analyzed by routine enzyme-linked immunosorbent assay techniques. Nineteen patients with chronic nonallergic sinusitis, 24 patients with seasonal allergic rhinitis, and 18 patients with nonallergic nasal polyposis were included in the study. Eight healthy, nonallergic probands served as control subjects. RESULTS: Significantly elevated concentrations of IL-5 (5-fold, P < .05) and IgE (15-fold, P < .01) were detected in nasal secretion of patients with allergic rhinitis (IL-5, 51.8 +/- 13.2 pg/mL; IgE, 41.9 +/- 20.9 kU/L) or nonallergic nasal polyposis (IL-5, 57.9 +/- 36.9 pg(mL; IgE, 40.5 +/- 20.2 kU/L) compared with controls (IL-5, 10.6 +/- 7.8 pg/mL; IgE, 2.8 +/- 0.5 kU/L) or with patients with chronic nonallergic sinusitis (IL-5, 16.5 +/- 13.2 pg/mL; IgE, 5.4 +/- 3.1 kU/L). There were no significant differences between patients with allergic rhinitis and those with nonallergic nasal polyposis. Concentrations of ECP were significantly elevated (sixfold, P < .01) in patients with allergic rhinitis (297.8 ng/mL +/- 173.1) compared with controls (52.4 +/- 28.0 ng/mL) or patients with chronic nonallergic sinusitis (44.8 +/- 40.1 ng/mL), whereas twofold higher concentrations (not significant) of ECP were observed in patients with nonallergic nasal polyposis (107.1 +/- 26.6 ng/mL). Significantly elevated concentrations of sICAM-1 in nasal secretion (threefold, P < .05) were detected only in patients with chronic nonallergic sinusitis (79.4 +/- 45.6 ng/mL). The elevated sICAM-1 nasal secretion values in this group correlated significantly (P < .05) to the serum values. CONCLUSIONS: Equally elevated concentrations of IL-5 and IgE in patients with allergic rhinitis and nonallergic nasal polyposis implicated similar pathogenic processes in both diseases. Whereas the pathogenesis of allergic rhinitis is IgE-specific, the pathogenesis of nasal polyps is not as clear. IL-5 was suggested to play a pivotal role in tissue eosinophilia, which was confirmed by data in the present study. Elevated concentrations of ECP were suggested to result from tissue eosinophilia--a characteristic of both diseases. Elevated concentrations of sICAM-1 in patients with chronic nonallergic sinusitis pointed to its key role in the recruitment of neutrophils into the inflamed tissue, whereas an important role in eosinophil recruitment was ruled out.     

基因重组γ干扰素在治疗变应性鼻炎中的作用

目的研究基因重组γ干扰素在治疗变应性鼻炎中的作用.方法采用随机对照研究方法将60例变应性鼻炎患者分成两组,每组30例,一组予常规脱敏治疗(对照组),另一组予常规脱敏治疗加基因重组γ干扰素治疗(实验组),6个月后比较两组的症状评分、血清白细胞介素-4(IL-4)、嗜酸粒细胞阳离子蛋白(ECP)水平.结果对照组治疗前、后症状评分分别为10.6±2.3和4.2±1.8,血清IL-4水平分别为(545.3±86.2)ng/L和(320.4±76.3)ng/L,ECP水平分别为(24.3±8.2)μg/L和(12.4±6.3)μg/L;实验组治疗前、后症状评分分别为10.8±2.7和3.5±1.6,血清IL-4水平分别为(547.8±84.6)ng/L和(280.4±87.3)ng/L,ECP水平分别为(25.1±7.7)μg/L和(10.4±5.1)μg/L.实验组治疗后症状评分、IL-4和ECP水平均低于对照组(均P<0.05).结论基因重组γ干扰素能改善变应性鼻炎症状,降低血清IL-4、ECP水平,在变应性鼻炎的治疗中发挥着免疫调节作用.     

Does pregnancy-associated plasma protein A have a role in allergic rhinitis?

BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A), also known as insulin-like growth factor binding protein 4 protease, is postulated to be a new inflammatory marker in various clinical situations such as cardiovascular events, dialysis, renal transplantation, and asthma. PAPP-A also is produced in high concentrations by trophoblasts during pregnancy. METHODS: We evaluated PAPP-A levels in allergic rhinitis patients and compared these with levels in healthy subjects. Thirty-one newly diagnosed allergic rhinitis patients and 29 healthy controls were included in the study. Serum PAPP-A, IgE, urea, creatinine, aspartate aminotransferase, creatine kinase (CK), CK-MB isoenzyme, total cholesterol, and triglyceride levels were determined. RESULTS: The serum PAPP-A level was significantly higher (p = 0.013) in the allergic rhinitis group (6.1 +/- 2.9 mU/L) than in the control group (4.5 +/- 1.7 mU/L). The PAPP-A level in patients with allergic rhinitis and asthma (6.1 +/- 2.3 mU/L) was not significantly different (p = 0.959) from that in patients with allergic rhinitis alone (6.1 +/- 3.3 mU/L). The serum PAPP-A level in allergic rhinitis patients who had turbinate hypertrophy (6.9 +/- 2.2 mU/L) had a tendency to be higher than that in patients who had no turbinate hypertrophy (5.5 +/- 3.2 mU/L); however, this difference was not statistically significant (p = 0.151). CONCLUSION: Increased PAPP-A activity may be involved in the inflammation and tissue remodelling that occurs in allergic rhinitis.     

Effects of corticosteroids on expression of interleukin-18 in the airway mucosa of a mouse model of allergic rhinitis

OBJECTIVES: In this study, we aimed to investigate the release and response of interleukin (IL)-18 to steroid treatment in a mouse model of allergic rhinitis. METHODS: BALB/c mice were sensitized systemically by intraperitoneal injection of ovalbumin and locally by ovalbumin inhalation. Dexamethasone sodium phosphate was given by intraperitoneal injection in the steroid treatment group. Symptom scores, eosinophil counts, and IL-18 concentrations in the nasal and lung lavage fluids were analyzed. RESULTS: The symptom scores and eosinophil counts of the negative control and steroid treatment groups were significantly lower than those of the positive control group (p < .01). The mean IL-18 concentrations in the nasal lavage fluid were not significantly different among the three groups (56.68 +/- 9.57,63.39 +/- 8.93, and 64.47 +/- 6.83 pg/mL, respectively). The IL-18 concentrations in the lung lavage fluid were significantly different between the positive control group and the steroid treatment group (430.75 +/- 154.54 and 69.94 +/- 14.26 pg/mL, respectively, p = .028). CONCLUSIONS: The IL-18 concentration was found to be increased in the lung lavage fluid, but not in the nasal lavage fluid, in a mouse model of allergic rhinitis. Increased IL-18 concentrations returned toward the previous concentrations after steroid treatment. These results suggest that the roles of IL-18 may be different in the pathogenesis of allergic rhinitis and the pathogenesis of asthma.     

鼻用皮质类固醇对鼻息肉中白细胞介素5 mRNA表达的影响

OBJECTIVE: To investigate the effect of intranasal glucosteroid treatment on the expression of interleukin (IL)-5 gene in nasal polyps. METHODS: Nasal polyps from topical steroid treated patients (n = 20) and untreated patients (n = 20) were investigated with the technique of mRNA in situ hybridization. RESULTS: The majority of IL-5 mRNA positive cells in nasal polyps were lymphocytes or eosinophils. No statistical significance was found in the densities of IL-5 mRNA positive cells between allergic patients [(12.6 +/- 4.6)/0.25mm2] and nonallergic patients [(14.3 +/- 4.1)/0.25mm2] (t = -0.775, P > 0.05). Compared with the control group [(13.9 +/- 4.2)/0.25mm2], the density of IL-5 mRNA positive cells was decreased in the steroid-treated group [(10. 2 +/- 3.1)/0.25mm2], and the difference reached statistical significance (t = 3.114, P < 0.01). CONCLUSIONS: These findings indicate that topical steroid treatment may suppress the IL-5 gene expression, and steroids may inhibit eosinophil functions.     

变应性鼻炎患者鼻腔灌洗液中细胞间黏附分子-1和白细胞介素-6水平及其与气道反应性的关系

OBJECTIVE: To investigate the relation between levels of intercellular adhesion molecule-1, interleukin-6 and airway hyperresponsiveness in patients with allergic rhinitis. METHODS: Fifty-four patients with allergic rhinitis (AR) and 20 controls were included in the study. The levels of intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in nasal lavage fluid, gathered 1 hour after specific allergen nasal provocation test (SANPT), were detected by sandwich enzyme-linked immunosorbent assay (ELISA) technique. The pulmonary function (FEV1) and nonspecific bronchial provocation test were measured in 54 patients with AR, 36 patients with AR and bronchial asthma (BA) and 20 controls. At the same time, the correlation between levels of ICAM-1 and IL-6 in nasal lavage fluid and pulmonary function (FEV1) was studied. RESULTS: The levels of ICAM-1 and IL-6 in nasal lavage fluid from patients with AR were (272.75 +/- 32.25) pg/ml and (52.11 +/- 16.54) pg/ml, significantly higher than those the controls, which were (158.82 +/- 33.88) pg/ml and (25.64 +/- 10.14) pg/ml (P < 0.01). The pulmonary function (FEV1) in patients with AR and BA was (78.82 +/- 7.41)%. It was obviously lower than that in patients with AR [(83.90 +/- 4.87)%], much lower than that in normal controls [(90.25 +/- 4.69)%]. The difference among them was significant. In patients with AR, the positive percentage of bronchial provocation test was 64.81%, in patients with AR and BA, it was 83.33% in normal controls, it was 0. The differences among them had very significant meaning. The levels of ICAM-1 and IL-6 in nasal provocation fluid had closely negative correlation with pulmonary function (FEV1), r = -0.7071, -0.6248, P < 0.01. CONCLUSIONS: The close correlation was observed in upper and lower airway for allergic inflammation. The pulmonary function of patients with AR was lower, and 64. 8% of them had airway hyperresponsiveness, so that they had the potent possibility to have bronchial asthma.     

白细胞介素6和肿瘤坏死因子—α在分泌性中耳炎渗出液中表达及…

Using enzyme-linked immunosorbant assay (ELISA), we measured levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in middle ear effusions (MEE) from patients with secretory otitis media (SOM) undergoing auripuncture to study the role of cytokines in the pathogenesis of the disease. Significant levels of IL-6 (> 62.5 ng/L) were found in 19 (86.36%) of 22 MEEs and those of TNF-alpha (> 37.5 ng/L) in 19 (70.37%) of 27 MEEs. The mean (+/- s) levels of IL-6 and TNF-alpha were 507.68 +/- 813.11 ng/L and 186.86 +/- 166.93 ng/L, respectively. It revealed that the shorter the course, the higher the concentration of IL-6 in MEE: the longer the course, the higher the concentration of TNF-alpha in MEE. These findings suggested that during the early stages of SOM, IL-6 might participate in the defensive reaction of organism, while TNF-alpha might be closely related to the persistence of SOM, resulting in an excessive inflammatory reaction with a potential for pathological changes. It is concluded that the immunological mechanisms probably play a significant role in the pathogenesis of SOM.