| Objective (1) To investigate the concentration, source and significance of serum interleukin-5 (IL-5) in children with allergic asthma. (2) To investigate the effect of IL-5 on eosinophilic inflammation in asthmatic airways in vivo. (3) To investigate the role of IL-5 in the mechanism of airway hyperresposiveness. (4) To investigate the effects of IL-5 on changes of activity and number of circulating eosinophils, as well as concentrations of serum IgE. (5) To investigate the effects of IL-5 on changes of soluble intracellar adhesion molecule-1 (sICAM-1) concentrations in induced sputum from allergic asthmatics.Methods (1) Sera were collected from children with allergic asthma, including both acute cases and remission cases, and health subjects. ELISA assay was adopted to detect the concentrations of IL 5 and soluble IL-2 receptor (sIL-2R), and immunoradioassay was used to detect the levels of eosinophil cationic protein (ECP). (2) Eight subjects with mild atopic asthma underwent initial bronchoscopy during which control bronchoalveolar lavage fluid (BALF) as well as bronchial mucosa were obtained, and at the same time, normal saline and IL-5 were administered to two sublobar segments separately. The second bronchoscopy was carried out and the samples from challenged sites were taken 24 h later. (3) The effects of inhaled IL-5 on airway responsiveness to methacholine and cell populations in induced sputum were studied in eight patients with allergic bronchial asthma using aplacebo-controlled study design. (4) Eight nonsmoking patients with allergic asthma were administered IL-5 by nebulization, total blood nuclear cell counts and differentials, as well as concentrations of ECP and IgE in serum were determined before, and at 2, 24, 48 h after inhalation, respectively. (5) Eight patients with allergic asthma and six non-allergic normal subjects were administered IL-5 by nebulization, and the concentrations of sICAM-1 in induced sputum from each subject were determined before, and at 2, 24, 48, 72 h after inhalation, respectively.Results (1) The levels of IL-5, ECP and sIL-2R were significantly raised during asthma attack when compared with those observed in normal controls;IL-5 and ECP levels were also significantly higher during asthma attack than those observed in stable asthma, with the difference of sIL-2R did not reach significant. In addition, the elevation of IL-5 was related to concentrations of ECP and sIL 2R. (2) The "total" eosinophils (BMK-13+ cells) and the "activated" eosinophils (EG2+ cells) in bronchial mucosa, the eosinophil numbers in BAL fluid, as well as ECP in BAL fluid from saline challenged segments were not different from those in unchallenged segments. However, a significant eosinophilia was observed in bronchial mucosa and BALF from IL-5 challenged-sites. Eosinophil activation, as assessed by secretion of ECP, was also increased significantly in bronchial mucosa and BAL fluid. (3) the inhalation of IL-5 did not alter lung function in allergic asthmatics. In the control experiments receiving vehicle, PC2o-Mch values did not change nor did the numbers of eosinophils or ECP sputum values changefrom baseline. In contrast, after IL-5 inhalation, PC2o-Mch fell down significantly. Accompanying this increased airway sensitivity was a significant eosinophilia and elevated concentrations of eosinophil cationic protein in induced sputum. (4) Eosinophil numbers in circulation increased after IL-5 inhalation, accompanying this significant blood eosinophilia was a significant elevation of serum ECP levels. However, IL-5 inhalation had no significant effect of levels of serum total IgE. (5) In allergic asthmatics, vehicle challenge was not able to cause any changes in sputum sICAM-1 concentrations. However, there were increases in sputum sICAM-1 concentrations after IL-5 inhalation, which increased with time significantly greater than baseline values, reaching a maximum at 48 h, and lasting no less than 72 h. The concentrations of sICAM-1 in sputum after IL-5 challenge exceeded levels that could be accounted for by passive transudation from the circulation, based upon the magnitude of increases in sputum albumin concentration.Conclusions (1) IL-5 is involved in the acute exacerbation of asthma, and may be related to chronic inflammation in the asthmatic airways. Our results suggested that IL-5 derived from activated lymphocytes. (2) IL-5 is capable of inducing eosinophil infiltration into the asthmatic airways, as well as the activation of infiltrating eosinophils. (3) IL-5 increases airway responsiveness and infiltration of activated eosinophils into the airway in patients with allergic bronchial asthma. (4) IL-5 not only induced a significant blood eosinophilia, but also resulted in the activation of circulating eosinophils. (5) IL-5 inhalation wascapable of inducing an elevation of sputum sICAM-1 concentration by stimulating its local release in allergic asthmatics, but not in non-allergic normal subjects.
|
PDF Full Text Request