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 function s, either alone or in combination with interleukin-4 (IL-4). These dru gs enhanced in a dose-dependent manner the IL-4-induced membrane and m RNA 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)-ch ain (CD18) of the leukocyte functional antigen (LFA(1)) family. This e ffect appeared to be restricted to CD11b (CR3) and CD11c (pp 150-95), because CD11a (LFA-1 alpha chain) was not modified. beta(2)-Adrenocept or stimulation was also found to potentiate the effect of IL-4 on CD11 b, 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/ant i-IgE immune complexes induced the release of free radicals nitric oxi de 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 pro duction of IL-6 and TxB(2) triggered by CD23 ligation. These results i ndicate that beta(2)-adrenoceptor stimulation potentiates in vitro the IL-4 -induced phenotypical and functional changes on monocytes and su ggest that such an interaction could occur in IgE-dependent immune rea ctions.