New clinical applications of xanthine derivatives: modulatory actions on leukocyte survival and function

The use of theophylline in the treatment of obstructive pulmonary diseases has diminished with the advent of new medications. However, its use as a second-line bronchodilator has been reconsidered in recent years. Theophylline is reported to have immunomodulatory actions that may account for its clinical effectiveness in the control of airway inflammation. Theophylline, even at low plasma concentrations, inhibits the late asthmatic reaction following allergen challenge. The apparent suppression of airway inflammation by theophylline reinforces findings from in vitro experiments (including our recent studies). Its immunomodulatory actions include inhibition of cytokine synthesis and release, inhibition of inflammatory cell activation, and acceleration of granulocyte apoptosis. On the basis of these findings, theophylline has been re-evaluated as a key drug for the long-term management of bronchial asthma, and new applications are proposed for the clinical use of xanthine derivatives. Here, we review some recent advances in the understanding of pharmacological actions and new applications of xanthine derivatives.