EFFECTS OF BETA(2) ADRENOCEPTOR AGONISTS ON T-CELL SUBPOPULATIONS

The aim of the present communication is to determine the effects of be ta(2) adrenoceptor agonists on growth and cytokine secretion using all ergen-specific T cells. Four beta(2) adrenoceptor agonists were admini stered at therapeutically relevant doses (salbutamol 1-2 mu M; salmete rol 0.03-0.06 mu M; terbutaline 0.56-1.12 mu M, and fenoterol 0.7-1.4 mu M to: a) Cultures of human peripheral mononuclear cells (PBMC) b) P ositively selected CD4(+) and CD8(+) subsets, c) Allergen-specific T-c ell lines (TCL). Drug effects on growth kinetics and the secretion of IL-4,IL-5, INF-gamma and IgE following T-cell stimulation were investi gated. Comparing the growth inhibitory effect of the 4 beta(2) agonist s at 2 different concentrations, using 12 PBMC, 10 CD4(+) and CD8(+) a nd 10 TCL cultures, the following patterns were observed: PBMC-, CD4()- and CD8(+)-cultures: salmeterol, followed by salbutamol and fenoter ol, was a more potent inhibitor than terbutaline. In long-term TCL-cul tures, salmeterol was the most potent drug, followed by fenoterol. No significant differences were observed between salbutamol and terbutali ne. TCL secretion of IL-4 and IL-5 (TH2 cytokines) was also significan tly inhibited. In one patient, INF-gamma, 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 stimulat ion, could be reduced by the drugs. The results showed that the beta(2 ) agonists could influence T-cell growth and function. The changes reg arding cell function were individual and related to T-cell phenotypes secreting TH1/THO or TH2 cytokines. These results suggest that adminis tration of beta(2) adrenoceptor agonists could be beneficial, not only for bronchodilation, but also for suppressing the underlying inflamma tory process dominated by TH2-like cytokine secretion.