Inhibition of natural killer cell activity by oral administration of theophylline

Asthmatic patients have a low incidence of malignancies, and this is possibly due to higher NK cell activity in this population. Because theophylline is used widely in this population, we evaluated the influence of theophylline on NK cell activity in vitro and in vivo. The NK cell activity was significantly inhibited by direct addition of concentrations of aminophylline that exceeded 5 x 10(-5) M. To test whether such an effect can be observed in vivo, we administered one sustained-release tablet of theophylline (400 to 500 mg twice daily) to five normal volunteers for seven days. Significant inhibition of NK activity was noted after administration (mean percentage of inhibition, 41.3 percent), but the serum concentrations observed gave a mean value of 2 x 10(-5) M, which was lower than that yielding the same degree of inhibition by direct addition in vitro (about 20 x 10(-5) M). These results suggest that long-term theophylline therapy may inhibit NK cell activity, and thus more information would be needed to determine the position of such therapy in the management of asthmatic patients.