Theophylline reduces histamine release during pollen-induced rhinitis

In an attempt to understand how theophylline achieves its in vivo therapeutic effect, a double-blind crossover study of the effect of theophylline on the immediate response of the upper airways to challenge with antigen was performed. Ten subjects with allergic rhinitis were challenged with increasing doses of antigen extract, and their responses were assessed by counting the number of sneezes and measuring the level of histamine, N-α-p-tosyl-l-arginine-methyl ester-esterase activity, and kinin in nasal secretions. One-week premedication with theophylline led to serum levels in the therapeutic range (8 to 21 μg/ml). There were significant reductions in both the physiologic response to antigen challenge and the appearance of mediators in secretions after drug administration as compared to placebo. These data suggest that theophylline, at therapeutic blood levels, achieves at least part of its in vivo efficacy by reducing the release of histamine and other mediators from mast cells/basophils.