Low-dose theophylline modulates T-lymphocyte activation in allergen-challenged asthmatics

Theophylline has been shown by several investigators to attenuate the late asthmatic response (LAR) to inhaled allergen, suggesting that it has antiinflammatory or immunomodulatory properties. We have, therefore, undertaken a double-blind, placebo-controlled study to examine the effects of low-dose theophylline on bronchoalveolar lavage (BAL) and blood T-lymphocyte profile and activation in asthmatics following antigen challenge and the development of a LAR. Peripheral blood and BAL samples were obtained from 17 subjects with mild atopic asthma before and after 6 weeks of treatment with either oral theophylline or placebo. The mean serum theophylline concentration achieved was 6.6 μg · mL^-1, which is below the currently accepted therapeutic range. Following theophylline therapy, there was a significant decrease in the number of BAL lymphocytes compared to placebo. On flow cytometric analysis of BAL cells, a significant loss of CD3+ T-lymphocytes, comprising both CD4+ and CD8+ subsets, was demonstrated. Moreover, there was a decrease in the number of BAL CD4+ T-cells expressing the activation marker very late activation antigen-1 (VLA-1), and an apparent reduction in human leucocyte antigen-DR (HLA-DR). Correspondingly, this was accompanied in the blood by an elevation in the proportion of activated CD4+ T-lymphocytes, in particular those expressing HLA-DR. These findings provide further evidence that theophylline has an anti-inflammatory action in asthma.