BETA(2)-ADRENOCEPTOR AGONISTS REGULATE THE IL-4-INDUCED PHENOTYPICAL CHANGES AND IGE-DEPENDENT FUNCTIONS IN NORMAL HUMAN MONOCYTES

The beta(2)-adrenoceptor agonists salbutamol and fenoterol were tested for their regulatory effects on human monocyte phenotype and functions, either alone or in combination with interleukin-4 (IL-4). These drugs enhanced in a dose-dependent manner the IL-4-induced membrane and mRNA expression of the low-affinity receptor for immunoglobulin E (IgE) (CD23), as well as the release of its soluble form, sCD23. Salbutamol and fenoterol alone elicited expression of the monomorphic beta(2)-chain (CD18) of the leukocyte functional antigen (LFA(1)) family. This effect appeared to be restricted to CD11b (CR3) and CD11c (pp 150-95), because CD11a (LFA-1 alpha chain) was not modified. beta(2)-Adrenoceptor stimulation was also found to potentiate the effect of IL-4 on CD11b, CD11c, and CD18 expression. In contrast, these agents alone did not alter the level of major histocompatibility complex class II and CD14 antigens or modify their respective up- and down-regulation by IL-4. Ligation of CD23 on IL-4-preincubated (CD23(+)) monocytes with IgE/anti-IgE immune complexes induced the release of free radicals nitric oxide and of the proinflammatory mediators IL-6 and thromboxane B-2(TXB(2)) Addition of salbutamol, inactive alone, potentiated the generation of superoxide anion and of nitric oxide generation, as well as the production of IL-6 and TxB(2) triggered by CD23 ligation. These results indicate that beta(2)-adrenoceptor stimulation potentiates in vitro the IL-4 -induced phenotypical and functional changes on monocytes and suggest that such an interaction could occur in IgE-dependent immune reactions.