The study of pathophysiology, early intervention, and treatment for virus-induced asthma using a gene microarray analysis

由于病毒诱导哮喘患者的嗜酸性粒细胞活化和细胞因子反应的相关信息很少，我们尝试检测呼吸道病毒，并检测急性哮喘和缓解期哮喘患者血清中各种细胞因子/趋化因子和嗜酸性粒细胞阳离子蛋白(ECP)的水平。同时采用多重微珠分析法(Bio-Rad)检测38例急性哮喘患者和51例缓解期哮喘患者外周血嗜酸性粒细胞计数、血清ECP浓度和17种细胞因子/趋化因子(IL-1J3、2、4、5、6、7、8、10、12、13、17、干扰素-γ、肿瘤坏死因子-α、粒-巨噬细胞集落刺激因子、巨噬细胞集落刺激因子、巨噬细胞趋化蛋白-1和巨噬细胞趋化因子-1β)。我们还利用基因芯片分析(Affymetrix)研究了哮喘患者嗜酸性粒细胞在人刺激下的高表达基因。在157例急性哮喘患者中，鼻病毒是Det…感染较多的有46例；RS病毒43例；肠道病毒18例；其他病毒18例；无病毒32例。急性发作期哮喘患者ECP、IL-5、IL-6、IL-8和IL-10水平显著高于缓解期哮喘患者，但嗜酸性粒细胞计数无明显变化。这些结果与鼻病毒诱导的哮喘和RS病毒诱导的哮喘的观察结果更相似，而不是稳定哮喘的结果。只有鼻病毒组的IL-5水平显著高于RS病毒组。最后，我们发现哮喘患者经人刺激的嗜酸性粒细胞中caspase 4、丝氨酸/苏氨酸激酶17b、趋化因子(C-C基序)配体5、趋化因子(C-C基序)受体1等基因表达上调。呼吸道病毒诱导的儿童哮喘的主要原因是鼻病毒和RS病毒。病毒诱导的哮喘，特别是鼻病毒诱导的哮喘，可能促进嗜酸性粒细胞的激活。此外，这些基因可能是哮喘嗜酸性炎症的治疗靶点。较少

Since little information is available on eosinophil activation and cytokine response in virus-induced asthma, we attempted to detect respiratory viruses and measure levels of various serum cytokines/chemokines, and eosinophil cationic protein (ECP) in acute as well as stable asthma.We detected viruses in nasal lavage obtained from patients with acute asthma using antigen detection kits or PCR followed by direct DNA sequencing analysis. We also measured peripheral eosinophil counts, concentrations of serum ECP, and 17 types of cytokines/chemokines (IL-1J3, 2, 4, 5, 6, 7, 8, 10, 12, 13, 17, IFN-γ, TNF-α, GM-CSF, G-CSF, MCP-1, and MIP-1β) using a multiplex beads-based assay (Bio-Rad) in 38 patients with acute asthma and in 51 patients with stable asthma who were not taking systemic corticosteroids. We also investigated the high expression gene in human stimulated eosinophils from patients with asthma using a gene microarray analysis (Affymetrix).Of the 157 acute asthma, rhinovirus was det … More ected in 46; RS virus, in 43; enterovirus, in 18; other viruses, in 18; and no viruses, in 32. The concentrations of ECP, IL-5, 6, 8, and IL-10, but not eosinophil counts, were significantly elevated in acute asthma as compared with those in stable asthma. These results were more similar to those observed in rhinovirus-induced asthma and RS virus-induced asthma than to those of stable asthma. Only the IL-5 level was significantly elevated in the rhinovirus group than in the RS virus. Finally, we found that several genes including caspase 4, serine/threonine kinase 17b, chemokine (C-C motif)ligand 5, chemokine (C-C motif) receptor 1 upregulated in human stimulated eosinophils obtained by asthmatic patients.The major causes of respiratory virus-induced childhood asthma were rhinovirus and RS virus.Virus-induced asthma, particularly those induced by rhinoviruses, might enhance eosinophil activation.Furthermore, these genes might be a therapeutic target for eosinophilic inflammation in asthma. Less