Rovina Nikoletta, Dima Efrossini, Bakakos Petros, Tseliou Eleni, Kontogianni Konstantina, Papiris Spyros, Koutsoukou Antonia, Koulouris Nikolaos G, Loukides Stelios
National and Kapodistrian University of Athens, 1st Department of Pulmonary Medicine, "Sotiria" District Chest Diseases Hospital, Athens Medical School, Greece.
National and Kapodistrian University of Athens, 1st Department of Pulmonary Medicine, "Sotiria" District Chest Diseases Hospital, Athens Medical School, Greece.
Respir Med. 2015 May;109(5):580-7. doi: 10.1016/j.rmed.2015.03.002. Epub 2015 Mar 19.
Severe refractory asthma (SRA) is characterized by persistent asthma symptoms, amplified airway inflammation despite treatment with high dose inhaled steroids and increased airway bacterial colonization. Interleukin (IL)-18 is a pleiotropic pro-inflammatory cytokine that modulates airway inflammation. Furthermore, as a product of the inflammasome, IL-18 is involved in host defence against viral and bacterial stimuli by modulating the immune response.
To determine IL-18 levels in sputum supernatants of patients with asthma and to investigate whether underlying severity affects its levels. Furthermore, possible associations with atopy and mediators and cells involved in the inflammatory process of the airways were examined.
Forty-five patients with mild intermittent asthma (21 smokers) and 18 patients with SRA in stable state were studied. All subjects underwent lung function tests, skin prick tests, and sputum induction for cell count identification. IL-18 and ECP levels were measured in sputum supernatants. Furthermore, sputum samples were examined for the commonest respiratory pathogens and viruses by real time polymerase chain reaction (RT-PCR).
Patients with SRA had significantly lower IL-18 levels in sputum supernatants compared to mild asthmatics (p < 0.001). Twelve out of eighteen patients with SRA were colonized by viruses and/or bacterial pathogens. IL-18 levels correlated with the percentage of macrophages (r = 0.635, p = 0.026) and inversely correlated with the percentage of neutrophils in sputum (r = -0.715, p = 0.009). No correlations were found between IL-18, ECP and the percentage of eosinophils in the sputum of SRA.
In SRA IL-18 is possibly involved in chronic airway inflammation through an eosinophil independent pathway. The decreased levels of IL-18 in SRA support the hypothesis of deregulated inflammasome activation, justifying the susceptibility of these patients for bacterial colonization or infection.
重度难治性哮喘（SRA）的特征为哮喘症状持续存在、尽管使用高剂量吸入性糖皮质激素治疗但气道炎症仍加剧以及气道细菌定植增加。白细胞介素（IL）-18是一种具有多种功能的促炎细胞因子，可调节气道炎症。此外，作为炎性小体的产物，IL-18通过调节免疫反应参与宿主对病毒和细菌刺激的防御。
测定哮喘患者痰液上清液中的IL-18水平，并研究潜在的严重程度是否会影响其水平。此外，还检查了与特应性以及参与气道炎症过程的介质和细胞之间可能存在的关联。
对45例轻度间歇性哮喘患者（21例吸烟者）和18例处于稳定状态的SRA患者进行了研究。所有受试者均接受了肺功能测试、皮肤点刺试验以及痰液诱导以进行细胞计数鉴定。测定痰液上清液中的IL-18和嗜酸性粒细胞阳离子蛋白（ECP）水平。此外，通过实时聚合酶链反应（RT-PCR）检查痰液样本中最常见的呼吸道病原体和病毒。
与轻度哮喘患者相比，SRA患者痰液上清液中的IL-18水平显著降低（p < 0.001）。18例SRA患者中有12例被病毒和/或细菌病原体定植。IL-18水平与巨噬细胞百分比相关（r = 0.635，p = 0.026），与痰液中中性粒细胞百分比呈负相关（r = -0.715，p = 0.009）。在SRA患者的痰液中，未发现IL-18、ECP与嗜酸性粒细胞百分比之间存在相关性。
在SRA中，IL-18可能通过嗜酸性粒细胞非依赖性途径参与慢性气道炎症。SRA中IL-18水平降低支持炎性小体激活失调的假说，这证明了这些患者易发生细菌定植或感染。
