Effects of theophylline, dexamethasone and salbutamol on cytokine gene expression in human peripheral blood CD4+ T-cells

Abstract

CD4+ T-cells are considered as pivotal in orchestrating the airway inflammation in asthma through the actions of their cytokines. Current hypothesis suggests that the anti-asthma effect of theophylline may be due to its anti-inflammatory actions, although the exact mechanisms remain unclear.The in vitro effect of theophylline on cytokine gene expression in peripheral blood CD4+ T-cells in normal subjects was compared with that of dexamethasone and salbutamol. CD4+ T-cells were cultured with phytohaemagglutin and phorbol myristate acetate in the presence of different concentrations of theophylline (10 -8 ±10 -3 M or 0.0018±180 mg . mL -1 ) in one group of subjects (n=8), dexamethasone (10 -9 ±10 -6 M or 0.39±390 ng . mL -1 ) in a second group (n=8) and salbutamol (10 -9 ±10 -4 M or 0.00058±58 mg . mL -1 ) in a third group (n=8). Gene expression of interleukin (IL)-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)-c was semiquantified by reverse transcription-polymerase chain reaction.Suppressed expression of IL-3 (36.9%), IL-4 (38.8%), GM-CSF (24.6%) and IFN-c (37.7%), but not of IL-5, was only seen with theophylline at a concentration of 10 -3 M (180 mg . mL -1 ) (p<0.05) and not at lower concentrations. In contrast, dexamethasone caused a dose-dependent suppression of transcription of all cytokines, with 39.5% for IL-3, 84.4% for IL-4, 40.6% for IL-5, 50.9% for GM-CSF and 31.8% for IFN-c at 10 -6 M (390 ng . mL -1 ) (p<0.05±0.001). Salbutamol did not suppress gene expression of any of the cytokines at the concentrations examined.These data suggest that cytokine gene expression of CD4+ T-cells is not affected at therapeutic concentrations of theophylline and salbutamol, but its suppression is likely to be an important mechanism underlying the therapeutic effect of corticosteroids in asthma.

(S,S)-Formoterol Increases the Production of IL-4 in Mast Cells and the Airways of a Murine Asthma Model

“…In our study, (S,S)-formoterol had no effect on IL-4 secretion in Jurkat human T cells in contrast to its stimulatory effect on IL-4 production in mast cells, suggesting that the effect of (S,S)-formoterol on IL-4 production is cell type-specific. Our results are consistent with Choy et al’s finding [22]that albuterol did not have any effect on the expression of the IL-4 gene in human peripheral blood CD4+ T cells.…”

Immune function in children under chemotherapy for standard risk acute lymphoblastic leukaemia – a prospective study of 20 paediatric patients

“…Furthermore, we could not confirm a cytokine dysregulation with a shift towards a preferential production of Th2 cytokines in our paediatric ALL‐cohort (Zhang et al , 2000). However, the lower production of IFNγ by T cells from patients treated with dexamethasone fits well with the known immunosuppressive effects of this steroid on T‐cell function (Choy et al , 1999) and could partly explain the increased rate of infectious complications in this patient population (Mantadakis et al , 2004). Interestingly, reduced IFNγ‐production was the only parameter associated with the application of dexamethasone while all other immune parameters, including TCR‐repertoire complexity and thymic function, were not affected by its use.…”

Theophylline, an old drug with multi-faceted effects: Its potential benefits in immunological liver injury in rats

“…Nie et al [37] described no significant change in the level of IFN-γ in the sputum of asthmatic patients after administration of low oral dose theophylline. Choy et al [6] demonstrated that an in vitro suppression effect of theophylline on IFN-γ expression in peripheral blood CD4 Tcells in normal subjects was only seen with high concentration of theophylline (10 −3 M) and not at low concentration.…”