支气管哮喘患儿治疗前后血清GM-CSF、IL-8和IL-6联检的临床意义

目的：探讨了支气管哮喘患儿血清GM—CSF、IL-8和IL-6水平的变化及意义。方法：应用放射免疫分析对32例支气管哮喘患儿进行了血清GM—CSF、IL-8和IL-6水平测定,并与30例正常健康儿作比较。结果：支气管哮喘患儿血清GM—CSF、IL-8和IL-6水平非常显著地高于正常儿组（P〈0．01）。经治疗3个月后则与正常儿比较无显著性差异（P〉0．05）。结论：血清GM—CSF、IL-8和IL-6水平的异常升高足支气管哮喘患儿发病的病理因素之一．有重要的临床价值。     

细胞粘附分子与支气管哮喘

粘附分子(Adhesion molecules,AMS)是一类介导细胞间粘附及细胞与细胞外基质粘附的糖蛋白,传递细胞间信息,调节细胞功能,在炎性细胞向气道炎区跨内皮转移和浸润中具有重要作用,是支气管哮喘发病机制中的重要活性物质[1],深入研究两者间的关系将为揭示哮喘的发病机制和制定相应的治疗措施提供理论基础.     

孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10水平的影响

目的:探讨孟鲁司特在支气管哮喘患者体内IL-6、IL-8和IL-10水平的影响。方法:应用放射免疫分析和酶联法对31例支气管哮喘患者应用孟鲁司特治疗前后血清IL-6、IL-8和IL-10水平的变化,并与35名正常健康人作比较。结果:支气管哮喘患者在治疗前血清IL-6、IL-8水平非常显著地高于正常人组(P<0.01),而IL-10水平显著地低于正常人组(P<0.01),经治疗2周后与正常人组比较仍有显著性差异(P<0.05)。结论:孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10有一定程度的调节作用,从而降低患者体内的炎症水平,促进病情缓解和好转。     

细胞因子诱导HepG2细胞ICAM—1表达的研究

目的 研究IFN-γ、TNF-a和IL-1对HepG2细胞细胞间粘附分子-1（ICAM-1）表达的影响。方法 用IFN-γ、TNF-a和IL-1在体外诱导HepG2细胞表达ICAM-1,并用细胞FLISA检测HepG2细胞ICAM-1表达水平。结果 未经刺激的HepG2细胞ICAM-1表达水平很低。TNF-a、IL-1、IFN-γ刺激后,HepG2细胞ICAM-1表达均明显增强,其表达水平与细胞因子浓度呈一定的剂量依赖关系;随着细胞因子刺激时间的延长,HepG2细胞ICAM-1表达也逐渐增多。结论IFN-γ、TNF-a和IL-1等细胞因子能诱导体外培养HepG2细胞ICAM-1增强表达。     

IL-2等6种细胞因子与儿童支气管哮喘关系的研究

观察急性发作期、激素治疗后缓解期支气管哮喘患儿血浆细胞因子的变化,探讨儿童支气管哮喘与细胞因子的关系。采用免疫分析技术对64例急性发作期支气管哮喘患儿、45例缓解期患儿及20例正常儿童血浆IL-2、sIL-2R、IL-4、IL-5、IL-8、TNF-α、IgE等细胞因子水平进行测定;用逆转录聚合酶键反应技术（RT-PCR）对外周淋巴细胞IL-4、IL-5mRNA表达进行定量分析。结果:（1）发作期哮喘患儿血浆IL-2、sIL-2R、IL-4、IL-5、IL-8、TNF-α和IgE水平均明显高于正常对照组（P值均<0.001）,以IL-4、IL-5和IgE变化最为明显,缓解期均明显下降,但IL-4、IL-5及IgE水平仍高于正常水平（P<0.01）。（2）发作期患儿外周淋巴细胞IL-4、IL-5mRNA表达增强,治疗缓解后减弱,同时血浆IL-4、IL-5分别与IL-4、IL-5mRNA呈明显正相关关系。结论:（1）本研究结果提示细胞因子的释放与哮喘的发作密切相关。（2）外周淋巴细胞IL-4、IL-5强表达以及血浆IL-4、IL-5高水平提示哮喘发作期Th2亚群的激活;同时IL-8和TNF-α的升高表明中性粒细胞和单核巨噬细胞可能参与哮喘的发作。（3）糖皮质激素抑制多种细胞因子的释放,可能是其治疗哮喘的主要机制。     

女性经前期复发性阿弗他溃疡患者血清IL-6、IL-8、TNF-α和sICAM-1的含量变化及其意义

目的:研究女性经前期复发性阿弗他溃疡(经前期RAU)患者血清中白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)和可溶性细胞间粘附分子-1(sICAM-1)的变化状况, 并探讨经前期RAU的发病机制。方法:用酶联免疫吸附双抗体夹心法(ELISA)检测女性经前期RAU患者外周血中IL-6、IL-8、TNF-α、sICAM-1的水平, 与正常对照组和无经前发作规律的女性RAU对照组相比。结果:经前期RAU患者的血清IL-6、IL-8、TNF-α水平不仅显著高于正常对照组(P＜0.01), 而且高于女性RAU对照组(P＜0.01)。而sICAM-1无明显变化。女性RAU患者血清中TNF-α亦高于正常对照组(P＜0.05)。结论:经前期RAU患者体内存在IL-6、IL-8、TNF-α介导的免疫功能异常, 可能对RAU局部损害起作用。     

慢性肾炎患者血清sIL—2R和IL—8的变化及意义

本研究用ＥＬＩＳＡ双抗体夹心法对慢性肾炎肾功能不全各期患者血清ｓＩＬ－２Ｒ和ＩＬ－８水平进行了测定。结果显示：（１）肾功能不全代偿期ｓＩＬ－２Ｒ水平显著高于健康人，提示此期存在Ｔ细胞异常活化。（２）氮质血症期ｓＩＬ－２Ｒ水平显著高于健康人和代偿期，与Ｓｃｒ呈显著正相关提示血清ｓＩＬ－２Ｒ水平可作为肾小球肾炎恶化的重要指标。     

可溶性细胞间粘附分子-1在慢性肾衰患者中检测的临床意义

可溶性细胞间粘附分子(Soluble Intercellular Adhesion Molecule-1,ICAM-1)为细胞粘附分子中可溶性免疫球蛋白超家族成员之一,其配体为淋巴细胞功能相关抗原-1(LFA-1)[1].已知感染是引起慢性肾衰血透患者死亡的重要原因[2].我们检测尿毒症血透患者血清、透析液中sICAM-1水平变化,目的是探讨其对机体免疫功能的影响.     

哮喘患者血清细胞因子的变化及其临床意义

目的探讨哮喘患者血清白细胞介素-25(IL-25)、白细胞介素-27(IL-27)在哮喘发展过程中的含量变化及其临床意义。方法分别选择64例急性加重期和临床缓解期哮喘患者,采用免疫散射比浊法测定血清中急性时相反应蛋白[铜兰蛋白(CER)、转铁蛋白(TRF)、α1-酸性糖蛋白(AAG)和结合珠蛋白(HP)]的浓度;ELISA法检测血清IL-25、IL-27浓度,并与30名健康对照者进行比较。并对急性加重期哮喘患者血清细胞因子IL-25、IL-27与急性时相反应蛋白(CER、TRF、AAG和HP)行相关性分析。结果哮喘患者临床缓解期组和急性加重期组HP、IL-25血清浓度均显著高于健康对照组(P<0.05),急性加重期较临床缓解组高(P<0.05);哮喘患者急性加重期TRF的含量显著低于健康对照组和临床缓解组(P<0.05),临床缓解期组TRF的含量出现上调,但与健康对照组比较无统计学意义(P>0.05);急性加重期哮喘患者血清IL-25、IL-27与急性时相反应蛋白(CER、TRF、AAG和HP)均无明显的相关性(P>0.05)。结论 HP能作为较好反映哮喘病情活动的指标,表明IL-25参与了哮喘的炎性病理过程,但其在哮喘炎性病理过程中起何具体作用有待进一步研究。     

支气管哮喘的细胞因子治疗进展

哮喘是一种慢性气道炎症性疾病,它的发生和发展与多种细胞因子密切相关.目前哮喘还没有有效的预防和治愈方法,细胞因子抑制剂已经作为潜在的治疗手段而被广泛研究.其中IL-4、IL-5、TNF-α抑制剂的临床研究已经取得了突破性的进展.IL-13和IL-9的临床试验正在研究中.对哮喘动物模型的大量研究发现了胸腺基质淋巴细胞生成素(TSLP),IL-17等新的相关细胞因子,这为哮喘细胞因子治疗提供了新的思路.而多种细胞因子抑制剂的联合使用也为治愈哮喘提供了可能.同时,哮喘个体化医疗的研究为逆转哮喘提供了有力保障.     

Interferon-gamma secretion of peripheral blood CD8+ T lymphocytes in patients with bronchial asthma: in vitro stimulus determines cytokine production.

It has been postulated that T lymphocytes orchestrate the chronic inflammation in bronchial asthma. In animal models, infiltration of CD8+ T lymphocytes into the bronchial mucosa prevented bronchial hyperresponsiveness and decreased early and late phase reaction. IFN-gamma antagonizes IL-4-dependent IgE production as well as IL-5-induced proliferation and activation of eosinophils. We therefore investigated the secretion of IFN-gamma of isolated CD8+ T lymphocytes from peripheral blood of patients with allergic asthma (n = 6) and from healthy controls (n = 7) in vitro. In this setting we compared the effect of stimulation with anti-CD3 antibodies with that of phorbol myristate acetate (PMA) and calcium-ionophore. As expected, CD8+ T lymphocytes from peripheral blood of healthy volunteers produced significantly more IFN-gamma in the presence of PMA and calcium-ionophore than after stimulation with anti-CD3 antibodies. However, in subjects with allergic asthma, IFN-gamma secretion of CD8+ T cells was significantly higher when incubated with anti-CD3 antibodies than after activation with PMA and calcium-ionophore. While IFN-gamma secretion of CD8+ T lymphocytes of patients with allergic asthma was lower than that of healthy controls in the presence of PMA/calcium-ionophore, it was significantly elevated when compared with normal controls after stimulation with anti-CD3 antibodies. Thus, potent activators of cytokine secretion, such as PMA and calcium-ionophore, induce a cytokine profile different from that induced by weaker stimulants, such as anti-CD3 antibodies. These findings have implications for further studies investigating cytokine production of inflammatory cells in vitro.     

Differences in cytokine production by peripheral blood mononuclear cells (PBMC) between patients with atopic dermatitis and bronchial asthma.

It is widely accepted that type 2 helper T (Th2) lymphocytes play a crucial role in the pathogenesis of atopic dermatitis (AD) as well as bronchial asthma (BA). We measured the amounts of IL-5 and interferon-gamma (IFN-gamma) produced by PBMC upon stimulation with house dust mite (HDM) or Candida albicans (CA) in 17 children (3-15 years) with AD, and compared these values with those of 16 children with BA. Although IL-5 production by PBMC upon stimulation with HDM in patients with AD was significantly higher than that in 13 non-atopic controls (geometric mean = 23.4 pg/ml versus 5.9 pg/ml, P < 0.05), it was significantly lower than that in patients with BA (177.8 pg/ml, P < 0.001). The amount of IL-5 produced by PBMC upon stimulation with CA was also significantly lower in patients with AD than in those with BA (7.2 pg/ml versus 100.0 pg/ml, P < 0.001). The production of IFN-gamma by PBMC stimulated with HDM or CA was also significantly lower in patients with AD than in those with BA (HDM 4. 3 pg/ml versus 12.6 pg/ml, P < 0.05; CA 6.5 pg/ml versus 60.3 pg/ml, P < 0.001). Consequently the ratio of IL-5 to IFN-gamma production was high not only in patients with BA but also in those with AD. These findings suggest that there are some differences in the regulation of in vivo cytokine production between patients with AD and those with BA, although a Th2-dominant profile is common to both.     

ICAM-1与支气管哮喘的研究进展

细胞间粘附分子-1(intercellularadhesionmolecule-1,ICAM-1)是免疫球蛋白(immunoglobulin,Ig)超家族成员之一,对白细胞牢固黏附和白细胞从血管中迁移到炎症组织部位起着关键作用.白细胞表面粘附分子与血管内皮细胞表面的粘附分子(如:ICAM-1)相互作用后可介导白细胞从血液循环中迁移到肺组织的炎症部位,这在支气管哮喘发病机制中起着重作用.本综述将简阐述ICAM-1及其表达调控在支气管哮喘中的研究进展.     

慢性肝病患者血清细胞因子变化与临床意义

目的：为探讨慢性乙型肝炎病毒性肝病患者血清细胞因子ＴＮＦ－α、ＩＬ－１、ＩＬ－６、ＩＬ－８活性变化及其在慢性肝病发生发展中的作用及临床意义。方法：采用ＥＬＩＳＡ法对慢性乙型肝炎（ＣＨ）、慢性乙型重型肝炎（ＣＳＨ）、乙型肝炎性肝硬化（ＨＣ）患者血清中细胞因子ＴＮＦ－α、ＩＬ－１、ＩＬ－６、ＩＬ－８活性进行了测定。结果：慢肝患者血清ＴＮＦ－α、ＩＬ－１、ＩＬ－６、ＩＬ－８水平明显高于健康对照组（Ｐ〈０     

Elevated levels of soluble ICAM-1 in sera from patients with bronchial asthma

We measured the levels of soluble intercellular adhesion molecule-1 (sICAM-1) in sera from patients with bronchial asthma. sICAM-1 levels in sera from atopic asthmatic patients in stable conditions were higher than in normal control subjects. Furthermore, the sICAM-1 levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These results suggest that higher levels of sICAM-1 in sera reflect the upregulation of ICAM-1 expression in allergic inflammation.     

Elevation of serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in bronchial asthma.

We have previously shown the elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) in patients with bronchial asthma during asthma attacks. In the present study, we extended our earlier study by measuring serum sVCAM-1 levels by ELISA in 45 patients with bronchial asthma (23 atopic and 22 non-atopic) during asthma attacks and in stable conditions in order to assess further the state of adhesion molecules in allergic inflammation of bronchial asthma. The levels of sVCAM-1 in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sVCAM-1 levels, serum tumor necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. The nature of change in serum TNF-alpha levels correlated with the nature of change in serum sVCAM-1 levels, but serum TNF-alpha levels did not correlate with serum sVCAM-1 levels. These results suggest that higher levels of sVCAM-1 during asthma attacks may reflect the up-regulation of VCAM-1 expression in allergic inflammation, and that a soluble form of VCAM-1 molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of VCAM-1 in vitro, however; the regulatory mechanism in the elevation of serum sVCAM-1 levels remains to be clarified.     

Increased adhesion to vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 of eosinophils from patients with asthma

Adhesion of peripheral blood eosinophil and neutrophil granulocytes to the endothelial cell adherence receptors E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 has been measured. The study included patients with allergic rhinitis, patients with mild allergic and nonallergic asthma, and healthy individuals; 10 persons were in each group. In addition, assay of eosinophil and neutrophil cell surface expression of the receptor complex CD11b/CD18 was performed. Increased eosinophil adhesion to vascular cell adhesion molecule-1 (p < 0.05) and intercellular adhesion molecule-1 (p < 0.05) was demonstrated in the patients with a more labile asthma, that is, a peak expiratory flow rate variability of more than 10%, suggesting a relationship to the degree of ongoing inflammation in the airways of the patients. The increased eosinophil adhesion was most probably due to a functional upregulation of the CD11b/CD18 and very late activation antigen-4 receptors, because the number of receptors measured as cell surface expression was unaltered. The increased eosinophil adhesion in the patients with high peak expiratory flow rate variability appeared independent of atopy. The increased adhesion was not entirely specific to the eosinophils, because neutrophils from patients with a peak expiratory flow rate variability of more than 10% also demonstrated increased adhesion to intercellular adhesion molecule-1 (p < 0.05) when compared with neutrophils from the patients with low peak expiratory flow rate variability. In conclusion, the demonstrated priming of eosinophil adhesion to vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 might be one contributing mechanism behind the selective accumulation of eosinophils in the lung tissue of patients with asthma. (J ALLERGY CLIN IMMUNOL 1995;96:941-50.)     

Increased secretion of IL-18 in vitro by peripheral blood mononuclear cells of patients with bronchial asthma and atopic dermatitis.

This study was performed to determine whether or not IL-18, formerly called IFN-gamma-inducing factor, is involved in the pathogeneses of allergic disorders. Peripheral blood mononuclear cells (PBMC) were obtained from patients with allergic bronchial asthma (BA), patients with atopic dermatitis (AD) and controls who did not have any allergic disease, and then cultured with lipopolysaccharide (LPS) or phytohaemagglutinin (PHA). The concentrations of IL-18, IFN-gamma and IL-13 in supernatant fluids were determined by enzymatic immunoassaying, and the expression of IFN-gamma messenger (m) RNA in the cells was measured by colorimetric microplate assaying. IL-18 secretion in the BA patients (geometric mean (gm) = 189 pg/ml) and AD patients (gm = 172 pg/ml) was significantly higher than that in non-allergic controls (gm = 118 pg/ml). In contrast, IFN-gamma secretion in the BA patients (gm = 7.3 IU/ml) and AD patients (gm = 6.8 IU/ml) was significantly lower than that in non-allergic controls (gm = 20.7 IU/ml). The amounts of IL-13 in supernatant fluids and IFN-gamma mRNA in cells were not statistically different among the BA patients, AD patients and non-allergic controls. The possible involvement of IL-18 in allergic disorders is discussed.     

IL-5, IL-8 and GM-CSF immunostaining of sputum cells in bronchial asthma and chronic bronchitis

Background: Granulocyte-macrophage colony stimulating factor (GM-CSF) and inlerleukin (IL)-5 or IL-8 have been .suggested to play an important role in the pathogenesis of eosinophilic airway inflammation in bronchial asthma or neutrophilic airway inflammation in chronic bronchitis, respectively, However, GM-CSF and IL-8 have biological activities to either eosinophils or neutrophils. Objective: To investigate the contribution of these cytokines to airway inflammation, we compared the cellular differential and immunolocalization of GM-CSF, IL-5 and IL-8 in sputum cells from patients with bronchial asthma and chronic bronchitis. Methods: Cytospins of sputum cells from 12 patients with bronchial asthma and 12 with chronic bronchitis were subjected to cellular differential counting and immunocytochemistry with antihuman GM-CSF, IL-5 and IL-8 antibody. Results: The predominant cells in bronchial asthma were eosinophils and lymphocytes, while those in chronic bronchitis were neutrophils. All cytokines examined were detected in either bronchial asthma or chronic bronchitis, although the percentage of GM-CSF and IL-5 positive cells in bronchial asthma (53.4 ± 6.0 [mean±sfm ]% and 9.7 ± 2.8%, respectively) was significantly higher than that in chronic bronchitis (11.4±2.5%; P < 0.001 and 1.7plusmn;0.3%; P < 0.007. respectively). In contrast, the percentage of IL-8 positive cells in chronic bronchitis (23.8 ± 7.0%) was significantly higher than that in bronchial asthma (7.7 ± 1.9%; P < 0.04). The cells positive for IL-5 were lymphocytes in bronchial asthma and chronic bronchitis. The cells positive for GM-CSF in bronchial asthma were predominantly eosinophils. while those in chronic bronchitis were monocytes/macrophages and neutrophils. In contrast, neutrophils are mainly positive for IL-8 in chronic bronchitis, while monocytes/macrophages and bronchial epithelial cells are positive for IL-8 in bronchial asthma. Conclusion: The immunochcmical comparison of GM-CSF and IL-8 localization in sputum cells between bronchial asthma chronic bronchitis suggests the differential regulation and roles of these cytokines in eosinophilic vs neutrophilic airway inflammation, resulting in the development of different types of airway inflammation.     

Elevation of serum soluble tumour necrosis factor (TNF) receptor and IL-1 receptor antagonist levels in bronchial asthma

The specific inhibitor for TNF-α activity, soluble form of the 55-kD TNF receptor (sTNF-RI) and soluble form of the 75-kD receptor (sTNF-RII), and the specific inhibitor for IL-1 activity, IL-1 receptor antagonist (IL-1Ra), have been identified. It has been shown that the levels of these inhibitors are elevated in plasma/serum and biological fluids in several diseases, and the protective and inhibitory effect of these inhibitors exist in several inflammatory diseases. In the present study, we measured serum levels of sTNF-RI, STNF-RII and IL-1Ra by ELISA in 36 patients with bronchial asthma (16 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of these inhibitors in allergic inflammation. The levels of sTNF-RI, sTNF-RII and IL-1Ra in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were obtained regardless of atopic status. These results suggest that higher levels of serum sTNF-RI, sTNF-RII and IL-1Ra may reflect up-regulation of TNF-R expression and IL-1Ra production in allergic inflammation, and sTNF-RI, sTNF-RII and IL-1Ra may contribute to regulating TNF-α- and IL-1-mediated production and development of allergic inflammation.