Limitations of corticosteroid effects in asthma: biochemical approach

Glucocorticosteroids (GCS) are the most effective treatment for bronchial asthma. Their mechanism of action, however, remains unknown, and a small proportion of asthmatic sufferers do not respond to their effects. GCS resistance in bronchial asthma may be secondary to altered bioavailability, a consistent polymorphism in the glucocorticoid receptor (GR), defective interaction with other transcription factors and/or deoxyribonucleic acid (DNA), or to a specific gene defect. Corticosteroid resistant bronchial asthma (CR asthma) cannot be explained on the basis of altered pharmacokinetics, or defective nuclear translocation or ligand binding of the GR, in CR subjects. Furthermore, peripheral blood monocytes (PBM) derived from asthmatic subjects generate a 3 Kd activity, which is proinflammatory in vitro for neutrophils and which is selectively inhibited by GCS in corticosteroid sensitive (CS) asthmatic subjects, with no inhibition seen in the CR group, suggesting a specific gene(s) defect.