Effects of β2 adrenoceptor agonists on T‐cell subpopulations

The aim of the present communication is to determine the effects of β 2 adrenoceptor agonists on growth and cytokine secretion using allergen-specific T cells. Four β 2 adrenoceptor agonists were administered at therapeutically relevant doses (salbutamol 1-2 μM; salmeterol 0.03-0.06 μM; terbutaline 0. 56-1.12 μM, and fenoterol 0.7-1.4 μM to: a) Cultures of human peripheral mononuclear cells (PBMC) b) Positively selected CD4 + and CD8 + subsets, c) Allergen-specific T-cell lines (TCL). Drug effects on growth kinetics and the secretion of IL-4,IL-5. INF-γ and IgE following T-cell stimulation were investigated. Comparing the growth inhibitory effect of the 4 β 2 agonists at 2 different concentrations, using 12 PBMC, 10 CD4 + and CD8 + and 10 TCL cultures, the following patterns were observed: PBMC-, CD4 + - and CD8 + -cultures: salmeterol, followed by salbutamol and fenoterol, was a more potent inhibitor than terbutaline. In long-term TCL-cultures, salmeterol was the most potent drug, followed by fenoterol. No significant differences were observed between salbutamol and terbutaline. TCL secretion of IL-4 and IL-5 (TH2 cytokines) was also significantly inhibited. In one patient, INF-γ secretion (TH1/THO cytokine) could be enhanced by drug administration. High IgE secretion, from 1% remaining B cells in one of the patients, following PHA+IL-2 stimulation, could be reduced by the drugs. The results showed that the β 2 agonists could influence T-cell growth and function. The changes regarding cell function were individual and related to T-cell phenotypes secreting TH1/THO or TH2 cytokines. These results suggest that administration of β 2 adrenoceptor agonists could be beneficial, not only for bronchodilation, but also for suppressing the underlying inflammatory process dominated by TH2-like cytokine secretion.