Eosinophil apoptosis caused by theophylline, glucocorticoids, and macrolides after stimulation with IL-5

Background: Glucocorticoids have long been used as the most potent drugs in the treatment of bronchial asthma. Data reported recently have led to the proposal that theophylline and macrolides have antiinflammatory effects. Objective: We examined the abilities of theophylline, glucocorticoids, and macrolides to counteract the prolongation of eosinophil survival caused by IL-5. Methods: purified guinea pig eosinophils were cultured in the presence or absence of human IL-5 and with or without the aforementioned drugs at various concentrations. The percentage of cells alive after 3 days in culture was determined. Results: Aminophylline (AM), methylpredrisolone (MP), erythromycin (EM), and clarithromycin (CAM) suppressed the IL-5 induced prolongation of eosinophil survival in a dose-dependent manner: The effects of these drugs on eosinophil survival were significantly greater at low concentrations of IL-5 than at high concentrations of IL-5. When eosinophils were cultured in the presence of IL-5 (I ng/ml) with physiologic concentrations of MP (10(-6) mol/L), AM (10(-4) mol/L), and either EM or CAM (both 10 mu g/ml) the effect of IL-5 was almost completely abolished and the morphologic changes in eosinophils observed by electron microscopy were consistent with apoptosis. DNA extracted from eosinophils cultured with IL-5 and each of the drugs was definitely fragmented. Conclusions: One mechanism of the effectiveness of these drugs is induction of eosinophil apoptosis. Some combination of these drugs may be useful in the treatment of bronchial asthma.