DIFFERENCES IN THE ANTIINFLAMMATORY EFFECTS OF THEOPHYLLINE AND PENTOXIFYLLINE - IMPORTANT FOR THE DEVELOPMENT OF ASTHMA THERAPY

Antiasthma drugs are now being re-evaluated for their anti-inflammator y effects. Theophylline is an immunomodulator; however, weak effects a nd the narrow therapeutic window make it a controversial drug. We comp ared 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 necrosi s factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleu kin-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 o n 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 th at of theophylline, and POF two times as potent. Inhibition of IFN-gam ma 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%) t han theophylline (7.5%). It is concluded that study of xanthine deriva tives in asthmatics might help the development of asthma therapy. POF seems to be an especially promising candidate.