Background: There is accumulating evidence that theophylline has anti-inflammatory or immunomodulatory effects. This may be, in part, mediated via an upregulation in the production of the anti-inflammatory cytokine interleukin (IL)-10. We determined whether low-dose theophylline (LDT) would increase the production of IL-10, and attenuate the production of proinflammmtory cytokines by alveolar macrophages. Methods: In a double-blind, placebo-controlled, crossover study involving 15 steroid-free patients with mild asthma, fiberoptic bronchoscopy and broncho-alveolar lavage (BAL) were performed at the end of the treatment and placebo periods. Alveolar macrophages were cultured in vitro, and we measured their release of IL-10, GM-CSF, and TNF-α. We also measured IL-10 production in whole blood together with the number of monocytes and T cells expressing intracellular IL-10 by flow cytometry. Results: LDT did not increase the production of IL-10, or attenuate the production of GM-CSF or TNF-α by alveolar macrophages. However, after theophylline treatment, there was a significant reduction in mean (SD) (95% CI) BAL eosinophil number from 3.4 (1.7)% (95% CI 2.4-4.4) to 1.7 (1.0)% (95% CI 1.1-2.3) compared with placebo (P ≤0.05). Similarly, there was no increase in whole-blood IL-10 release or in the number of monocytes and T cells expressing intracellular IL-10 after treatment. Conclusions: LDT has an anti-inflammatory effect in asthma; however, this effect is not mediated via the production of IL-10 or the attenuation of GM-CSF or TNF-α. The mechanisms of theophylline activity remain to be determined.
Low-dose theophylline does not exert its anti-inflammatory effects in mild asthma through upregulation of interleukin-10 in alveolar macrophages
CARAMORI, Gaetano;
2001
Abstract
Background: There is accumulating evidence that theophylline has anti-inflammatory or immunomodulatory effects. This may be, in part, mediated via an upregulation in the production of the anti-inflammatory cytokine interleukin (IL)-10. We determined whether low-dose theophylline (LDT) would increase the production of IL-10, and attenuate the production of proinflammmtory cytokines by alveolar macrophages. Methods: In a double-blind, placebo-controlled, crossover study involving 15 steroid-free patients with mild asthma, fiberoptic bronchoscopy and broncho-alveolar lavage (BAL) were performed at the end of the treatment and placebo periods. Alveolar macrophages were cultured in vitro, and we measured their release of IL-10, GM-CSF, and TNF-α. We also measured IL-10 production in whole blood together with the number of monocytes and T cells expressing intracellular IL-10 by flow cytometry. Results: LDT did not increase the production of IL-10, or attenuate the production of GM-CSF or TNF-α by alveolar macrophages. However, after theophylline treatment, there was a significant reduction in mean (SD) (95% CI) BAL eosinophil number from 3.4 (1.7)% (95% CI 2.4-4.4) to 1.7 (1.0)% (95% CI 1.1-2.3) compared with placebo (P ≤0.05). Similarly, there was no increase in whole-blood IL-10 release or in the number of monocytes and T cells expressing intracellular IL-10 after treatment. Conclusions: LDT has an anti-inflammatory effect in asthma; however, this effect is not mediated via the production of IL-10 or the attenuation of GM-CSF or TNF-α. The mechanisms of theophylline activity remain to be determined.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
