THEOPHYLLINE SUPPRESSES THE RELEASE OF TUMOR-NECROSIS-FACTOR-ALPHA BY BLOOD MONOCYTES AND ALVEOLAR MACROPHAGES

The purpose of this study was to evaluate the effect of theophylline on tumour necrosis factor-alpha (TNE-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 theophyline, 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 mu m (41+/-5.9% of controls) and at 50 mu m (59+/-4.8% of controls), while the inhibitory activity of theophylline at 10 mu m (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 tbe 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.