ROLE OF CYCLIC-AMP IN THE MODULATION OF IGE PRODUCTION BY THE BETA(2)-ADRENOCEPTOR AGONIST, FENOTEROL

We have previously demonstrated that the beta(2)-adrenoceptor agonist, salbutamol, potentiates the effect of interleukin-4 (IL-4) on immunog lobulin E (IgE) production by human peripheral blood mononuclear cells (PBMC). This study was undertaken to further define the activities of these drugs and the role of cyclic-adenosine monophosphate (cAMP) in the modulation of IgE production. Our results indicate that fenoterol (1 mu M) potentiated IL-4-induced IgE production and IgE messenger rib onucleic acid (mRNA) expression. Moreover, this effect was associated with an increase in intracellular cAMP levels. The activities of this drug on IgE production were mimicked by cell permeable cAMP analogues, such as dibutyryl-cAMP (db-cAMP) (100 mu M) or Sp-AMP (10 mu M). The potentiating effect of fenoterol on IgE production was markedly inhibi ted in the presence of protein kinase A (PKA) inhibitors: H8 (10 mu M) and Rp-AMP (10 mu M), suggesting that its effects are likely to depen d on the activation of the cAMP pathway. Additionally, the potentiatin g effect of fenoterol was also blocked in the presence of indomethacin . Fenoterol potentiated IL-4-induced IgE production from purified B-ce lls activated through their CD40 antigen. This effect was associated w ith an increase in cellular viability. Therefore, the activities of th is drug on PBMC are likely to be mediated by the activation of another cellular type. Taken together, these results show that fenoterol pote ntiates the IL-4-induced IgE production via the cAMP pathway, but that this enhancement could not be explained by a direct effect on B-lymph ocytes.