中度及重度哮喘气道细胞因子差异性比较
2008/04/30
一些有关重度哮喘的研究提出炎症的持续和变化可能与疾病严重程度有关。然而在中度和重度哮喘气道内组织，与嗜酸细胞和中性粒细胞性炎症相关的主要细胞因子和趋化因子的表达是否存在差异现在还不明确。为比较中－重度哮喘患者气道组织内有代表性的Th-1 (IFN- )和Th-2 (IL-4, IL-5) 细胞因子以及中性粒及嗜酸细胞相关的趋化因子 (IL-8 and eotaxin)的表达形式。Joanne Shannon等人将重度哮喘（24例）及中度哮喘组（26例）分别进行呼吸训练、诱导痰、NO呼气试验以及气管镜检查。然后通过免疫组化表达气道壁上皮及上皮下易感蛋白。
结果显示重度哮喘患者症状更明显，FEV1值更低，且痰中中性粒细胞(p = 0.007)和嗜酸细胞(p = 0.001)增多更明显。两组间NO呼气试验无明显差别。和中度哮喘组比，重度组IL-8和 IFN- 表达增加而IL-4表达减少(p 均< 0.001)。嗜酸细胞活化趋化因子和IL-5表达两组间无差别。
本试验证明重度哮喘患者痰中中性粒细胞增多和嗜酸细胞增多更明显，且气道内细胞因子和趋化因子的表达也不同于中度哮喘。中性粒细胞增高可能与IL-8的过度表达有关，而本研究结果未说明两组间嗜酸细胞的差异与IL-5和嗜酸细胞活化因子表达有关。
结果显示重度哮喘患者症状更明显，FEV1值更低，且痰中中性粒细胞(p = 0.007)和嗜酸细胞(p = 0.001)增多更明显。两组间NO呼气试验无明显差别。和中度哮喘组比，重度组IL-8和 IFN- 表达增加而IL-4表达减少(p 均< 0.001)。嗜酸细胞活化趋化因子和IL-5表达两组间无差别。
本试验证明重度哮喘患者痰中中性粒细胞增多和嗜酸细胞增多更明显，且气道内细胞因子和趋化因子的表达也不同于中度哮喘。中性粒细胞增高可能与IL-8的过度表达有关，而本研究结果未说明两组间嗜酸细胞的差异与IL-5和嗜酸细胞活化因子表达有关。
（于娜 中国医科大学附属第一医院呼吸内科 110001 摘译）
(Chest. 2008; 133:420-426)
Differences in Airway Cytokine Profile in Severe Asthma Compared to Moderate Asthma*
Joanne Shannon, MD; Pierre Ernst, MD; Yasuhiro Yamauchi, MD; Ronald Olivenstein, MD; Catherine Lemiere, MD; Susan Foley, MD; Leo Cicora, RT; Mara Ludwig, MD; Qutayba Hamid, MD, PhD and James G. Martin, MD, DSc
Abstract
Background: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]- ) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma.
Methods: Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry.
Results: Subjects with severe asthma were more symptomatic, had a lower FEV1, and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN- expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups.
Conclusion: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.
Key Words: cytokines • immunology • inflammation
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