Antiasthma drugs are now being re-evaluated for their anti-inflammatory effects.
Theophylline is an
immunomodulator; however, weak effects and the narrow therapeutic window make it a controversial
drug. We compared the immunomodulatory potencies of
theophylline with those of the
xanthines pentoxifylline (POF) and A802715. Using a whole-blood, cell-culture system, we studied the effects on the release of
tumor necrosis factor-alpha (
TNF-alpha),
interferon-gamma (IFN-gamma), and
interleukin-6 (IL-6) in six healthy subjects, and, in granulocyte
suspensions, the effects on the release of
reactive oxygen species (ROS). We also studied the influence of a 14-day treatment with
theophylline or POF on the release of the
cytokines named above in 14 asthmatics. We found that equimolar concentrations of A802715 most effectively inhibit ROS generation, followed by POF; the effects of
theophylline were weakest. A802715-inhibited release of
TNF-alpha was four times as potent as that of
theophylline, and POF two times as potent. Inhibition of IFN-gamma by A802715 was three times as potent, and by POF two times. Neither
drug influenced
IL-6 release. After a 14-day treatment of asthmatics, POF proved to inhibit
TNF-alpha release more effectively (by 44.3%) than
theophylline (7.5%). It is concluded that study of
xanthine derivatives in asthmatics might help the development of
asthma therapy. POF seems to be an especially promising candidate.