Glucocorticoids

The therapeutic, anti-inflammatory properties of glucocorticoids were recognized over forty years ago, when a striking improvement was observed following treatment with cortisone in patients with arthritis [1]. Since then, numerous chemical modifications have been made to the 4-ring steroid skeleton to improve anti-inflammatory potency, increase duration of activity, increase glucocorticoid relative to mineralocorticoid activity or reduce side-effects by increasing local efficacy relative to systemic activity. A defining characteristic of asthma in man is the presence of airway reactivity to both specific allergens and a wide range of non-specific physical and chemical stimuli. This phenomenon is well established and was demonstrated experimentally over 70 years ago [2, 3]. Although the pathogenesis underlying the hyperreactivity of airways smooth muscle in asthma is still to be fully elucidated, it is becoming increasingly clear that numerous cell types, mediators and cytokines contribute to the epithelial damage and restructuring in the airway wall which takes place during the progression of the disease [4, 5]. In turn, the anti-inflammatory treatment with glucocorticoids modulates the transcription of cytokines which dictate the composition of inflammatory cells which invade the airways [6], and induces the formation of proteins such as lipocortins (annexins) [7] which inhibit the formation of bronchoactive and vascoactive lipid mediators. Suppression of airway inflammation with glucocorticoids then reduces bronchial hyperreactivity with a concomitant reduction in asthma symptoms [8].