Effects of theophylline on inflammatory cells and cytokines in asthmatic subjects: a placebo-controlled parallel group study.

The anti-inflammatory effects of oral theophylline on cells in bronchial biopsies of symptomatic atopic asthmatic subjects were investigated. Following a 2 week run-in period, asthmatic subjects were randomly assigned to either placebo (n=11) or theophylline (n=15). Bronchial biopsies were taken at fibre-optic bronchoscopy at the beginning and end of a 6 week period, during which subjects took placebo or theophylline medication at a dose intended to produce therapeutic concentrations. Nine of the placebo subjects and 12 of the theophylline subjects completed the study. Improvement in asthma control was seen in the theophylline-treated group. The mean (SD) theophylline blood level at the end of the study was 10.9 (6.0) microg x mL-1. A significant decrease in interleukin (IL)4 expression from 1.38 to 1.04 cells x mm-2 (<0.05) and a trend to a reduction in IL-5 from 1.29 to 0.48 cells x mm-2 (NS) were seen in biopsies from the theophylline-treated group compared with placebo, although there was no change in mast cell numbers (judged by tryptase expression). A decrease in epithelial CD8+ cells from 2.60 to 0.53 cells x mm-1 of surface (<0.05) was noted. This study shows an anti-inflammatory effect of theophylline in asthmatic bronchi, both in cell numbers and in the expression of IL-4, believed to be an important cytokine in the pathophysiology of asthmatic inflammation. We speculate that theophylline induces downregulation in vivo of cytokine production, accounting for the known inhibitory effect of theophylline on the late asthmatic reaction.