Cytokine networks in the pathogenesis of bronchial asthma: implications for therapy

Bronchial asthma is characterised by a multicellular inflammatory process in the airways. The bronchial inflammation is orchestrated by a network of cytokines and growth factors which includes those encoded by the GM-CSF/IL-4/IL-5 gene cluster on chromosome 5. Their cellular origins are diverse and include both inflammatory and structural cells in the airways. The efficacy of glucocorticoids in the therapy of bronchial asthma may include the ability to disrupt these cytokine networks. The failure of glucocorticoids to provide benefit in some asthmatic patients may be caused by an excess of pro-inflammatory transcription factors which sequester the glucocorticoid receptor (GR), thereby preventing it from exerting its anti-inflammatory effects. Progress is being made in the elucidation of the molecular regulation of the transcription of TH2 cytokine genes. These novel insights may provide future strategies for therapeutic intervention in asthma.