Expression of Interleukin 9 in the Lungs of ?Transgenic Mice Causes Airway Inflammation,Mast Cell Hyperplasia,and Bronchial Hyperresponsiveness

Interleukin (IL)-9, a pleiotropic cytokine produced by the Th2 subset of T lymphocytes has been proposed as product of a candidate gene responsible for asthma. Its wide range of biological functions on many cell types involved in the allergic immune response suggests a potentially important role in the complex pathogenesis of asthma. To investigate the contributions of IL-9 to airway inflammation and airway hyperresponsiveness in vivo, we created transgenic mice in which expression of the murine IL-9 cDNA was regulated by the rat Clara cell 10 protein promoter. Lung selective expression of IL-9 caused massive airway inflammation with eosinophils and lymphocytes as predominant infiltrating cell types. A striking finding was the presence of increased numbers of mast cells within the airway epithelium of IL-9–expressing mice. Other impressive pathologic changes in the airways were epithelial cell hypertrophy associated with accumulation of mucus-like material within nonciliated cells and increased subepithelial deposition of collagen. Physiologic evaluation of IL-9–expressing mice demonstrated normal baseline airway resistance and markedly increased airway hyperresponsiveness to inhaled methacholine. These findings strongly support an important role for IL-9 in the pathogenesis of asthma.     

骨髓与支气管哮喘嗜酸性粒细胞增多症的关系研究进展

产生于骨髓的嗜酸性粒细胞(Eos)在哮喘气道炎症中发挥重要作用.骨髓的造血机制构成了哮喘气道炎症形成过程的活性组分,如骨髓嗜酸性粒细胞及其祖细胞数量的增加;骨髓细胞表达致炎因子如IL-5 mRNA、蛋白质和IL-5受体等.治疗哮喘的药物如糖皮质激素能抑制骨髓嗜酸性粒细胞形成.骨髓和肺组织一样,可能成为抗哮喘治疗的另一重要靶器官.     

Alterations in blood eosinophil morphology, binding capacity for complexed IgG and kinetics in patients with tropical (filarial) eosinophilia

As the significance of the eosinophilia which is found in some patients with chronic filarial infections is unknown, blood eosinophils were studied in seven patients with tropical (filarial) eosinophilia who had blood eosinophil counts between 5·2 and 56·6 × 10⁹/1. In six of these patients over 20% of the eosinophils were vacuolated, and degranulated eosinophils were found in the three patients with the most severe illness. In four patients serum eosinophil cationic protein levels were raised, and serial studies in two showed that they returned to normal after treatment with diethylcarbamazine. In addition, an increased proportion of eosinophils in these patients were able to bind to complexed IgG suggesting that they were responding to stimuli in the blood, and in one patient the blood eosinophil half-time clearance was prolonged. Labelled cells were cleared into the spleen, liver and bone marrow. These findings support the hypothesis that in patients with tropical (filarial) eosinophilia, blood eosinophils are induced to release their granule constituents into the circulation. It is suggested that these secretion products may interact with microfilariae, and may give rise to some of the clinical features of chronic filarial infections.     

A case of angiolymphoid hyperplasia with eosinophilia (ALHE) of the upper lip

Angiolymphoid hyperplasia with eosinophilia (ALHE) is clinically characterized by intradermal or subcutaneous papules and/or nodules usually occurring in young adults. Lesions in the oral mucosa are extremely rare. We report a case and review the literature of ALHE cases involving the oral mucosa. A 40-year-old man presented with a painless, 20 x 20 mm, submucosal nodule on the upper lip. Histological examination of lip biopsy specimens revealed an increase in many small vessels. The vascular walls consisted of prominent endothelial cells with a histiocytoid appearance, which protruded into the lumen. Many eosinophils and lymphocytes were also seen around the vessels. The diagnosis of ALHE was made from the above findings.     

Sclerosing mucoepidermoid carcinoma with eosinophilia of the salivary glands

We encountered two cases of low malignant mucoepidermoid carcinoma with scanty cellular atypism which originated in the parotid or submandibular gland and was characterized by marked fibrosis and eosinophilic infiltration within tumor tissue despite the predominance of the squamous component. Here we report these two cases and provide a review of the literature. We believe that clinically these two tumors with stromal fibrosis and eosinophilic infiltration have a low malignant potential, although histological examination revealed a scanty mucus-producing epithelial component. Therefore, we consider this type of tumor as a new subtype of mucoepidermoid carcinoma. A low-malignant mucoepidermoid carcinoma with stromal fibrosis and eosinophilic infiltration, as described in these two cases, may be misdiagnosed as a highly malignant mucoepidermoid carcinoma or squamous cell carcinoma because of its histologically scanty mucus-producing epithelial component. The objective of this study was to clarify their differences and to discuss the rendering of an accurate histological diagnosis, the degree of malignancy in relation to prognosis prediction, and the choice of therapy. In addition, we propose regarding this type of tumor as a new subtype of mucoepidermoid carcinoma.     

Dexamethasone reduces lung eosinophilia,and VCAM-1 and ICAM-1 expression induced by Sephadex beads in rats

Airway eosinophilia is one of the key pathophysiologic features in asthma. The endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1), have previously been shown to play a crucial role in eosinophil recruitment into the inflamed airway. We have investigated the effects of dexamethasone on eosinophilia into the bronchoalveolar lavage fluid, and the upregulation of VCAM-1 and ICAM-1 expression, measured by immunoblotting, induced by i.v. injection of Sephadex beads into rats. The beads significantly increased the lung eosinophilia, and expression of VCAM-1 and ICAM-1 in the lung. Pretreatment with dexamethasone (0.1 to 2 mg/kg i.p.) strongly inhibited all the airway inflammatory events in a dose-dependent manner. In conclusion, glucocorticoids may be potent inhibitors of lung eosinophilia, at least in part, due to the prevention of the upregulation of VCAM-1 and ICAM-1 expression.     

万古霉素致DRESS综合征22例文献分析

目的:分析万古霉素致伴嗜酸性粒细胞增多和系统症状的药疹综合征(DRESS综合征)的发生规律及特点,为安全用药提供参考。方法:检索国内外库收载的万古霉素致DRESS综合征文献进行分析。结果:共筛选出有效个案报道15篇,22例患者,其中男14例,女8例,青少年2例。用药至发生DRESS综合征的平均时间为3周。临床表现主要为皮疹、发热、嗜酸性粒细胞增多并累及多器官损伤,最常见受累的器官为肝脏(16例,72.7%)。结论:临床医师应了解万古霉素致DRESS综合征的规律和特点,加强用药监测,以便及时发现和处理DRESS综合征。