Theophylline suppresses the release of tumour 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 (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.
Spatafora
M
M
Istituto di Medicina Generale e Pneumologia, Università degli Studi, Palermo, Italy.
Chiappara
G
G
Merendino
A M
AM
D'Amico
D
D
Bellia
V
V
Bonsignore
G
G
D000818:Animals; D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013806:Theophylline