Inhibitory activity of fenoterol on Dermatophagoides-, Parietaria-, tetanus-toxoid-, and Candida albicans-stimulated blood mononuclear cells: Differences in beta(2)-adrenoreceptor stimulation but not in cell apoptosis

beta(2)-adrenoreceptor agonists have the ability to downregulate in vitro t he proliferative response of peripheral blood mononuclear cells (BMCs). Thi s activity could be related to a variety of beta(2)-adrenoreceptor-mediated functions, including induction of cell apoptosis in activated T-cells. To test this hypothesis, BMCs from atopic subjects, sensitized to house dust m ites (Dermatophagoides [Der p]) and/or to Parietaria were incubated with fe noterol 10(-8)-10(-5) M) in the presence of (a) purified allergen extracts (Der p [5 mu g/mL] or Parietaria 15 mu g/mL]) or (b) antigens (tetanus toro id [1 mu g/mL] or Candida albicans [5 x 10(5) bodies/ mL]). The BMC prolife ration was assessed by [H-3] thymidine incorporation and cell apoptosis was assessed by evaluating DNA fragmentation by a fluorescence technique, usin g propidium iodide. In cultures stimulated with Der p or with Parietaria, f enoterol induced a dose-dependent inhibition of BMC proliferation, signific ant also at the lowest concentration tested (10(-8) M) (p < 0.05, each comp arison). In contrast, the inhibitory activity of the drug on tetanus-toxoid -stimulated BMCs was significant only at the highest dose tested (10(-5) M) (p < 0.05), whereas no effect was seen when BMCs were stimulated with C, a lbicans extract (p > 0.05). The different inhibitory efficacy of fenoterol appeared to be related to the degree of activation of beta(2)-adrenorecepto rs on the different BMC populations that responded to the different stimuli . Indeed, in the presence of fenoterol (10(-6) and 10(-5) M), a significant increase in cyclic adenosine monophosphate (cAMP) levels was seen in Der p - or Parietaria-stimulated cells (p< 0.05; each comparison), but not in cel l cultures stimulated with tetanus toroid or with C. albicans extracts (p > 0.05; each comparison). Finally, the percentage of cells with fragmented D NA was lower in cultures stimulated with Der p or Parietaria than in those stimulated with tetanus toroid or C. albicans, and the presence of fenotero l did not modify cell apoptosis (p > 0.05; each comparison). Thus, the diff erent inhibitory activity of fenoterol on BMCs activated by allergens (Der p or Parietaria) or by antigens (tetanus toroid or C. albicans) seems to be related to differences in beta(2)-adrenoreceptor expression and/or functio n in the different antigen-specific T-cell subsets, but it is not influence d by changes in cell apoptosis.