Synergistic effect of theophylline and procaterol on interleukin-5-induced degranulation from human eosinophils

Inhibiting the release of toxic granule proteins from eosinophils is a possible means of treating allergic inflammation. This study was performed to examine whether procaterol and theophylline, commonly used bronchodilators in asthma, inhibit eosinophil degranulation induced by interleukin (IL)-5. Purified eosinophils from patients with asthma were incubated with IL-5 for 24 hr in the presence of theophylline, procaterol, combinations of theophylline and procaterol, or dexamethasone. Levels of eosinophil-derived neurotoxin (EDN) in the supernatants were measured with radioimmunoassay. Theophylline inhibited IL-5-induced release of EDN in a concentration-dependent manner. Procaterol inhibited degranulation only at high concentrations. However, procaterol at 10(-9) M and 10(-8) M, which are physiologic concentrations, together with theophylline at 10(-5) M, which is a concentration commonly found in the serum of patients receiving low-dose theophylline, inhibited degranulation by 43.8%. This finding indicates that theophylline and procaterol have synergistic effects. The inhibition was comparable to that with dexamethasone at 10(-9) M. Our results suggest that a combination of low-dose theophylline and procaterol exhibits antiinflammatory effects in asthma by inhibiting eosinophil-effector functions.