EOSINOPHIL APOPTOSIS CAUSED BY THEOPHYLLINE, GLUCOCORTICOIDS, AND MACROLIDES AFTER STIMULATION WITH IL-5

Background: Glucocorticoids have long been used as the most potent dru gs in the treatment of bronchial asthma. Data reported recently have l ed to the proposal that theophylline and macrolides have antiinflammat ory effects. Objective: We examined the abilities of theophylline, glu cocorticoids, and macrolides to counteract the prolongation of eosinop hil survival caused by IL-5. Methods: purified guinea pig eosinophils were cultured in the presence or absence of human IL-5 and with or wit hout the aforementioned drugs at various concentrations. The percentag e of cells alive after 3 days in culture was determined. Results: Amin ophylline (AM), methylpredrisolone (MP), erythromycin (EM), and clarit hromycin (CAM) suppressed the IL-5 induced prolongation of eosinophil survival in a dose-dependent manner: The effects of these drugs on eos inophil survival were significantly greater at low concentrations of I L-5 than at high concentrations of IL-5. When eosinophils were culture d 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 m u g/ml) the effect of IL-5 was almost completely abolished and the mor phologic changes in eosinophils observed by electron microscopy were c onsistent with apoptosis. DNA extracted from eosinophils cultured with IL-5 and each of the drugs was definitely fragmented. Conclusions: On e mechanism of the effectiveness of these drugs is induction of eosino phil apoptosis. Some combination of these drugs may be useful in the t reatment of bronchial asthma.