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

Eur Respir J. 1999 Nov;14(5):1106-12. doi: 10.1183/09031936.99.14511069.


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 microg x mL(-1)) in one group of subjects (n=8), dexamethasone (10(-9)-10(-6) M or 0.39-390 ng x mL(-1)) in a second group (n=8) and salbutamol (10(-9)-10(-4) M or 0.00058-58 microg x 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)-gamma was semiquantified by reverse transcription-polymerase chain reaction. Suppressed expression of IL-3 (36.9%), IL4 (38.8%), GM-CSF (24.6%) and IFN-gamma (37.7%), but not of IL-5, was only seen with theophylline at a concentration of 10(-3) M (180 microg x 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-gamma at 10(-6) M (390 ng x 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Albuterol / pharmacology*
  • Anti-Inflammatory Agents / pharmacology*
  • Asthma / drug therapy
  • Bronchodilator Agents / pharmacology*
  • CD4-Positive T-Lymphocytes / drug effects*
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Dexamethasone / pharmacology*
  • Electrophoresis, Agar Gel
  • Gene Expression / drug effects*
  • Humans
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Theophylline / pharmacology*


  • Adrenergic beta-Agonists
  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • Cytokines
  • RNA, Messenger
  • Dexamethasone
  • Theophylline
  • Albuterol