Theophylline and selective phosphodiesterase inhibitors as anti-inflammatory drugs in the treatment of bronchial asthma.

Theophylline has been in clinical use for the treatment of bronchial asthma and other respiratory diseases for well over 50 yrs. Over this time, a considerable body of evidence has accumulated to show that this drug has a wide range of pharmacological actions, in addition to the well-recognized action on airway smooth muscle function. Current evidence suggests that part of the therapeutic value of theophylline in the treatment of asthma is by virtue of an anti-inflammatory or immunomodulatory effect, although the actual mechanism of action remains unclear. It has been proposed that the observed anti-inflammatory effects of theophylline could be attributed to phosphodiesterase (PDE) inhibition, and recently the type III and IV isoenzymes have been characterized in a number of inflammatory cells. This article reviews the evidence that theophylline and the newer more selective type IV PDE isoenzyme inhibitors can inhibit the activation of inflammatory cell types, such as T-lymphocytes, eosinophils, mast cells and macrophages, in vitro. The evidence supporting the ability of theophylline and selective PDE IV isoenzyme inhibitors to modify allergic inflammation both in animal models and clinical asthma is also discussed. We conclude that theophylline possesses important anti-inflammatory and immunomodulatory activity and that, in light of this evidence, it is timely to reconsider the place of theophylline in the treatment of asthma.