Spatafora M, Chiappara G, Merendino A M, D'Amico D, Bellia V, Bonsignore G
Istituto di Medicina Generale e Pneumologia, Università degli Studi, Palermo, Italy.
Eur Respir J. 1994 Feb;7(2):223-8. doi: 10.1183/09031936.94.07020223.
The purpose of this study was to evaluate the effect of theophylline on tumour necrosis factor-alpha (TNF-alpha) release by human blood monocytes (BMo), and rat BMo and alveolar macrophages (AM). BMo and AM were incubated in the absence or presence of theophylline, and the cell-free supernatants were harvested and tested for TNF-alpha activity by bioassay. Theophylline dose-dependently reduced TNF-alpha release by human BMo: significant inhibition was observed at 100 microns (41 +/- 5.9% of controls) and at 50 microns (59 +/- 4.8% of controls), while the inhibitory activity of theophylline at 10 microns (71 +/- 8.9% of controls) was not statistically significant. This activity was maximal at 2 h and declined at 4 h (59 +/- 5.2% of controls) and 24 h (89 +/- 3.1% of controls). Northern analysis performed on ribonucleic acid (RNA) extracted from human BMo demonstrated that theophylline was able to reduce TNF-alpha gene expression. Comparable levels of inhibition of TNF-alpha release were observed on rat BMo and AM (rat BMo 42 +/- 4.9% of controls; rat AM 38 +/- 1.7% of controls), suggesting that BMo and AM are equally susceptible to suppression of TNF-alpha release induced by theophylline. These results indicate that theophylline suppresses TNF-alpha release by mononuclear phagocytes. Since TNF-alpha is involved in the pathogenesis of bronchial hyperresponsiveness and asthma, our results suggest that the therapeutic activity of theophylline might be partly related to its effect on TNF-alpha release.
本研究的目的是评估茶碱对人血单核细胞（BMo）、大鼠BMo和肺泡巨噬细胞（AM）释放肿瘤坏死因子-α（TNF-α）的影响。将BMo和AM在不存在或存在茶碱的情况下进行孵育，收集无细胞上清液，并通过生物测定法检测TNF-α活性。茶碱剂量依赖性地降低人BMo释放TNF-α：在100微摩尔（对照组的41±5.9%）和50微摩尔（对照组的59±4.8%）时观察到显著抑制，而茶碱在10微摩尔时的抑制活性（对照组的71±8.9%）无统计学意义。这种活性在2小时时最大，在4小时（对照组的59±5.2%）和24小时（对照组的89±3.1%）时下降。对从人BMo提取的核糖核酸（RNA）进行的Northern分析表明，茶碱能够降低TNF-α基因表达。在大鼠BMo和AM上观察到类似水平的TNF-α释放抑制（大鼠BMo为对照组的42±4.9%；大鼠AM为对照组的38±1.7%），表明BMo和AM对茶碱诱导的TNF-α释放抑制同样敏感。这些结果表明，茶碱抑制单核吞噬细胞释放TNF-α。由于TNF-α参与支气管高反应性和哮喘的发病机制，我们的结果表明，茶碱的治疗活性可能部分与其对TNF-α释放的影响有关。
