Asthma is one of the most chronic and morbid diseases affecting children worldwide. Cytokines are very important mediators of bronchial inflammation which is directly associated with asthma. Because of the intense and intricate interaction of cytokine networks, it is imperative that a comprehensive profile of cytokine gene expression be determined. Eosinophils are the principal cells involved in allergic inflammation. T cell cytokines IL-3, IL-5 and GM-CSF activate eosinophils which once activated can synthesize these cytokines themselves, thus creating chronic perpetual eosinophil activation with resultant destruction to the surrounding lung epithelia by release of toxic granules. Eosinophil cytokine receptors are a very significant components of the cytokine communication system and may regulate eosinophil recruitment. Therefore, a profile of the above cytokine receptor mRNA levels would provide a more comprehensive picture of the role of cytokines in bronchial inflammation. Eosinophils will be collected from blood samples of large atopic asthmatic families. The reverse transcriptase polymerase chain reaction will be used to detect mRNA in eosinophils for both cytokines and their receptors in atopic asthmatics, asthmatics, atopics, and nonatopic/nonasthmatic subgroups within families. Northern blot analysis will be performed on the PCR products. Additionally modulation of cytokine receptors by glucocorticoids and cromolyn (agents used in the treatment of asthma) will be evaluated Flow Cytometrically. Segregation analysis will be performed using cytokine, cytokine receptor mRNA levels and receptor density as phenotypes of bronchial inflammation. These gene products may be critical sites for therapeutic targeting in the war against asthma morbidity and mortality.
