Entzian P, Bitter-Suermann S, Burdon D, Ernst M, Schlaak M, Zabel P
Forschungszentrum Borstel, Medizinische Klinik, Germany.
Allergy. 1998 Aug;53(8):749-54. doi: 10.1111/j.1398-9995.1998.tb03970.x.
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.
目前正在对平喘药物的抗炎作用进行重新评估。茶碱是一种免疫调节剂；然而，其作用较弱且治疗窗狭窄，这使其成为一种有争议的药物。我们比较了茶碱与黄嘌呤类药物己酮可可碱（POF）和A802715的免疫调节效力。我们使用全血细胞培养系统，研究了六种健康受试者中它们对肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和白细胞介素-6（IL-6）释放的影响，以及在粒细胞悬液中对活性氧（ROS）释放的影响。我们还研究了茶碱或POF 14天治疗对14名哮喘患者上述细胞因子释放的影响。我们发现，等摩尔浓度的A802715最有效地抑制ROS生成，其次是POF；茶碱的作用最弱。A802715抑制TNF-α释放的效力是茶碱的四倍，POF是茶碱的两倍。A802715抑制IFN-γ释放的效力是茶碱的三倍，POF是茶碱的两倍。两种药物均未影响IL-6的释放。对哮喘患者进行14天治疗后，POF被证明比茶碱（7.5%）更有效地抑制TNF-α释放（44.3%）。结论是，对哮喘患者中黄嘌呤衍生物的研究可能有助于哮喘治疗的发展。POF似乎是一个特别有前景的候选药物。
