Zhou Qing-tao, Sun Yong-chang, Yao Wan-zhen
Department of Respiratory Medicine, Peking University Third Hospital, Beijing 100083, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2005 Sep;28(9):630-4.
OBJECTIVE: To investigate the characteristics of airway inflammation in severe asthma and the association with interleukin-17 (IL-17). METHODS: Sixteen patients with mild persistent asthma, 14 patients with moderate persistent asthma and 18 patients with severe persistent asthma, as well as 15 normal control subjects, were included in this study. At baseline, asthma symptom score was recorded, and lung function was measured. Induced sputum was obtained and processed for cell differential and the supernatant was assayed for the concentrations of IL-17 and IL-8 by sandwich enzyme-linked immunosorbent assay (ELISA), eosinophil cationic protein (ECP) by the immuno-CAP system, and neutrophil myeloperoxidase (MPO) by a colorimetric method, and the values were normalized to the protein content. Then 15 mild to moderate and 15 severe asthmatic patients received inhaled corticosteroid (Pulmicort, Astra-Zeneca) therapy for 4 weeks, and the above measurements were repeated. RESULTS: The percentage of sputum eosinophils and the level of ECP were significantly increased in mild [0.0670 +/- 0.0740, (155 +/- 91) x 10(-6) g/g protein], moderate [0.0830 +/- 0.0440, (180 +/- 83) x 10(-6) g/g protein] and severe [0.1240 +/- 0.1430, (191 +/- 87) x 10(-6) g/g protein] asthmatic patients, as compared to the normal controls [0.0000 +/- 0.0010, (44 +/- 25) x 10(-6) g/g protein, P < 0.01)]; but there was no significant difference among mild, moderate and severe asthma (P > 0.05). On the contrary, the percentage of sputum neutrophils was significantly increased in patients with severe asthma (0.589 +/- 0.203) as compared to patients with mild (0.455 +/- 0.154) and moderate (0.449 +/- 0.194) asthma and normal controls (0.313 +/- 0.134, P < 0.01). The level of MPO was also increased in severe asthma [(31 +/- 10 ) U/g protein] as compared to mild [(12 +/- 4) U/g protein] and moderate [(22 +/- 7) U/g protein] asthma and normal controls [(10 +/- 4) U/g protein, P < 0.01]. The sputum level of IL-17 in severe, moderate asthma [(264 +/- 137) x 10(-9) g/g protein, (172 +/- 65) x 10(-9) g/g protein] was significantly higher than those in mild asthma [(126 +/- 52) x 10(-9) g/g protein] and normal controls [(56 +/- 20) x 10(-9) g/g protein, P < 0.01]. As compared to the normal controls [(83 +/- 36) x 10(-9) g/g protein], the level of IL-8 in severe asthma [(531 +/- 321) x 10(-9) g/g protein] was significantly increased (P < 0.01), and those in mild [(410 +/- 181) x 10(-9) g/g protein] and moderate [(438 +/- 148) x 10(-9) g/g protein] asthma were also increased, although the difference was not statistically significant (P > 0.05). The level of IL-17 was correlated positively with IL-8, neutrophils and MPO (r = 0.525, 0.349, 0.602, all P < 0.01). After steroid therapy, the percentage of eosinophils, the levels of ECP, MPO, IL-17 and IL-8 decreased significantly in all patients combined, but the percentage of neutrophils remained unchanged (P > 0.05) and still significantly higher in severe asthmatic patients (0.642 +/- 0.157) as compared to mild and moderate asthmatic patients (0.394 +/- 0.147, P < 0.01). CONCLUSIONS: Airway neutrophilia is a feature of severe asthma. The IL-17/IL-8 pathway may be involved in the initial neutrophil influx into the airways.
目的：探讨重度哮喘气道炎症的特征及其与白细胞介素-17（IL-17）的关系。 方法：本研究纳入16例轻度持续性哮喘患者、14例中度持续性哮喘患者、18例重度持续性哮喘患者以及15名正常对照者。在基线时，记录哮喘症状评分并测量肺功能。获取诱导痰并进行细胞分类处理，采用夹心酶联免疫吸附测定法（ELISA）检测上清液中IL-17和IL-8的浓度，采用免疫化学发光法检测嗜酸性粒细胞阳离子蛋白（ECP），采用比色法检测中性粒细胞髓过氧化物酶（MPO），并将这些值标准化为蛋白质含量。然后，15例轻度至中度哮喘患者和15例重度哮喘患者接受吸入性糖皮质激素（普米克，阿斯利康）治疗4周，并重复上述测量。 结果：与正常对照者[0.0000±0.0010，（44±25）×10⁻⁶ g/g蛋白质，P<0.01]相比，轻度[0.0670±0.0740，（155±91）×10⁻⁶ g/g蛋白质]、中度[0.0830±0.0440，（180±83）×10⁻⁶ g/g蛋白质]和重度[0.1240±0.1430，（191±87）×10⁻⁶ g/g蛋白质]哮喘患者痰液嗜酸性粒细胞百分比和ECP水平显著升高；但轻度、中度和重度哮喘之间无显著差异（P>0.05）。相反，与轻度（0.455±0.154）、中度（0.449±0.194）哮喘患者及正常对照者（0.313±0.134，P<0.01）相比，重度哮喘患者痰液中性粒细胞百分比显著升高（0.589±0.203）。与轻度[（12±4）U/g蛋白质]、中度[（22±7）U/g蛋白质]哮喘及正常对照者[（10±4）U/g蛋白质，P<0.01]相比，重度哮喘患者MPO水平也升高[（31±10）U/g蛋白质]。重度、中度哮喘患者痰液IL-17水平[（264±137）×10⁻⁹ g/g蛋白质]显著高于轻度哮喘患者[（126±52）×10⁻⁹ g/g蛋白质]及正常对照者[（56±20）×10⁻⁹ g/g蛋白质，P<0.01]。与正常对照者[（83±36）×10⁻⁹ g/g蛋白质]相比，重度哮喘患者IL-8水平[（531±321）×10⁻⁹ g/g蛋白质]显著升高（P<<0.01），轻度[（410±181）×10⁻⁹ g/g蛋白质]和中度[（438±148）×10⁻⁹ g/g蛋白质]哮喘患者IL-8水平也升高，尽管差异无统计学意义（P>0.05）。IL-17水平与IL-8、中性粒细胞及MPO呈正相关（r = 0.525、0.349、0.602，均P<0.01）。激素治疗后，所有患者合并的嗜酸性粒细胞百分比、ECP、MPO、IL-17和IL-8水平均显著下降，但中性粒细胞百分比保持不变（P>0.05），且重度哮喘患者（0.642±0.157）仍显著高于轻度和中度哮喘患者（0.394±0.147，P<0.01）。 结论：气道中性粒细胞增多是重度哮喘的一个特征。IL-17/IL-8途径可能参与了中性粒细胞最初流入气道的过程。
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