Effect of Nedocromil Sodium on Leukotrienes and Platelet-Activating Factor Release in Asthmatic Children

Abstract

Airway inflammation is the most important component of asthma. Leukotrienes (LTB₄, LTB-C₄, LTB-D₄, LTB-E₄) and platelet-activating factor (PAF) play an important role in this inflammation. The pulmonary and peripheral leukocytes of asthmatics have a high potency of mediator-releasing activity after specific stimuli, and plasma levels of these are higher than in healthy controls. Nedocromil sodium (NES) is an inhaled anti-inflammatory drug and its inhibitory effect on inflammatory or epithelial cells has been demonstrated. The aim of this study was to determine whether inhaled NES affects plasma levels and release of PAF and leukotrienes from peripheral leukocytes of asthmatic children that were stimulated by house dust mites (as a specific allergen). Twenty-eight children (9 to 15 years of age) with atopic bronchial asthma were included in the study. They consisted of two age- and sex-matched groups (14 patients in the treatment group [group I]; 14 patients in the control group [group II]). Group I patients received inhaled NES (12 mg/d) for 12 weeks. Blood samples were drawn in the pre- and post-treatment periods. The measurements of plasma levels and secreted mediators levels after stimulation by house dust mites were performed with highpressure liquid chromatography (HPLC) and radioimmunoassay (RIA) methods. There were no significant differences between pretreatment plasma levels and secreted leukotrienes and PAF values of both groups. At the end of the study, significant decreases in plasma and in vitro stimulated LTB₄, LT-C₄, LT-D₄, LT-E₄, and PAF levels in group I were observed. There were no changes in the group II values. These in vivo and in vitro results suggest that NES is an effective anti-inflammatory drug for controlling childhood asthma by decreasing the high levels of inflammatory mediator release and immune cell activation.