Abstract
Corticosteroids are usually highly effective in the control of asthma. However, a small proportion of patients are corticosteroid-insensitive (CI) and may present considerable management problems. Long-acting β2-adrenergic agonists (LABA) affect corticosteroid action by enhancing glucocorticoid receptor activation. In this study, we investigated the effect of salmeterol on corticosteroid sensitivity in 6 CI severe asthma patients and compared with those of 12 normal subjects(NR). Peripheral blood mononuclear cells (PBMCs) were stimulated with TNF-α for 16 h in the presence or absence of dexamethasone (10-11–10-6 M) with or without salmeterol (10-8M). Interleukin(IL)-8 levels in supernatant were measured by ELISA. The IC50 value of dexamethasone on IL-8 production in patients with CI asthma was significantly higher than those in normal healthy volunteers (IC50: NR: 23.3±40 nM, CI asthma: 196.9 ±92nM, p=0.0017), suggesting CI patients were approximately 9 times more corticosteroid insensitive than NR. Add-on treatment of salmeterol completely restored dexamethasone sensitivity in CI asthma (IC50: CI asthma with salmeterol; 37.6±30 nM, p=0.0043) though salmeterol did not enhance corticosteroid sensitivity in NR. These results suggest that salmeterol is preferentially effective in corticosteroid sensitivity in CI asthma and may be beneficial for the treatment of CI asthma patients.