Mucosal inflammation in severe glucocorticoid-dependent asthma

Abstract

CD69 surface expression on human lung eosinophils after segmental allergen provocation. P. Julius, W. Luttmann, B. Knoechel, C. Kroegel, H. Matthys, J.C. Virchow Jr. #ERS Journals Ltd 1999. ABSTRACT: CD69 expression on eosinophils is observed in asthma and has been proposed as a marker of eosinophil activation. The role of allergens in the in vivo regulation of CD69 expression on eosinophils, however, remains incompletely understood. It was therefore investigated whether CD69 expression on eosinophils can be induced by allergen provocation in vivo.Ten allergic asthmatics were studied by segmental allergen provocation. Two segments of the right and left lung were challenged with allergen or saline. CD69 expression was determined by flow cytometry and concentrations of interleukins were analysed by enzyme-linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid.Expression of CD69 on BAL eosinophils in the segments lavaged 10 min following saline instillation (28.38.8 specific mean fluorescence (SMF)) was not significantly different to segments lavaged 10 min after allergen (80.221.8 SMF) and segments lavaged 18 h after saline challenge (87.223.3 SMF). However, CD69 expression on eosinophils increased significantly 18 h after allergen challenge (128.621.9 SMF, p<0.03) which was accompanied by elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations (114.942.9 pg . mL -1 , p<0.05). CD69 expression on eosinophils and GM-CSF concentrations correlated 18 h following allergen provocation (r=0.7, p<0.025).These results suggest that in allergic asthma there is an allergen dependent, endobronchial upregulation of eosinophil activation as assessed by CD69 expression on eosinophils.

Bronchial angiogenesis in severe glucocorticoid-dependent asthma

“…In a previous study it has been shown that severe asthma is characterized by increased numbers of CD25+ T-cells and relatively low eosinophil counts [11]. Why sensitized T-cells specifically accumulate in the airways of these patients is uncertain.…”

“…The primary goal of this and previous studies [11] was to investigate whether differences in VCAM expression could account for the differences in inflammatory cell profile between severe and mild asthmatics [11], and the authors therefore specifically selected patients who represented the two extremes of the disease spectrum. Previous studies have already shown that treatment of mild and moderately severe asthmatics with glucocorticoids is associated with a marked depletion of eosinophils and downregulation of T-lymphocyte activation with no differences in the expression of ICAM-1 and E-selectin [9].…”

“…Whilst the expression of ICAM-1 may not be upregulated per se, the increased density of vessels expressing ICAM-1, however, may enhance the influx of inflammatory cells and in particular activated T-cells in the airways from severe asthmatics and explain some of the recently described differences in the mucosal inflammatory profile between severe and mild asthma [11]. Because VLA-4 expression is restricted to eosinophils and lymphocytes, VCAM-1 has been implicated in the selective eosinophil diapedesis that characterizes atopic asthma [7].…”

“…Studies on bronchial biopsy specimens obtained from mild asthmatics have demonstrated constitutive expression of I-CAM-1 and, to a lesser extent, E-selectin on the bronchial microvasculature, which was not significantly different from normal subjects [9,10]. The authors have recently demonstrated an increase in the number of T-cells expressing the activation marker CD25 (interleukin (IL)-2 receptor) in bronchial biopsies from clinically unstable glucocorticoid-dependent asthmatics in comparison to mild asthmatics and normals [11]. However, this was not associated with raised eosinophil counts possibly secondary to the immunosuppressive actions of glucocorticoids.…”

Low-dose methotrexate treatment in severe glucocorticoid-dependent asthma: effect on mucosal inflammation and in vitro sensitivity to glucocorticoids of mitogen-induced T-cell proliferation

“…A proportion of these patients is found to be relatively resistant to the anti-inflammatory effects of glucocorticoids as judged by the reduced suppressive effects of dexamethasone on the proliferative response of peripheral blood mononuclear cells (PBMC) to the mitogen phytohaemagglutinin (PHA) [4] and increased peripheral blood T-cell activation [5]. Recently the authors have extended these observations to the bronchial mucosa by demonstrating the existence of increased mucosal T-cell activation in severe glucocorticoid-dependent asthmatics as compared to mild asthma and healthy control subjects [6]. In addition, increased concentrations of free interleukin (IL)-8 have been found in serum of severe asthmatics who were dependent on high doses of inhaled and in most cases systemic glucocorticoids [7].…”