Theophylline inhibits integrin-dependent eosinophil superoxide production

Theophylline has been proposed as a drug that is able to reduce eosinophil activation in asthma. We tested the hypothesis that it can interfere with the integrin-mediated stimulation of eosinophil function. Eosinophils from healthy donors were triggered by monoclonal antibodies to beta1- and beta2-integrins in the presence of different concentrations of theophylline: 4.3 microg/mL (2.4 X 10(-5) M) 13 microg/mL (7.2 X 10(-5) M) 26 microg/mL (1.4 X 10(-4) M), and 43 microg/mL (2.4 X 10(-4) M), respectively. The level of activation was evaluated by assaying O2- generation. A statistically significant inhibition (p < 0.05) of O2- generation was observed with the different concentrations of theophylline when eosinophils were triggered via very late antigen 4 (VLA-4), lymphocyte function antigen 1 and the common beta2-chain. No effect of theophylline on O2- generation was observed in phorbol-myristate-acetate-stimulated eosinophils. These results suggest that theophylline can interfere with the eosinophil activation triggered by ligation of beta1- and beta2-integrins. This effect of theophylline possibly may play a relevant role in the inhibition of eosinophil infiltration and activation at the sites of allergic reactions.