Effect of cyclic AMP-elevating agents on human spontaneous IgE synthesis in vitro

The cyclic AMP (cAMP)-elevating substances dibutyryl-cAMP (dbcAMP), isoproterenol and theophylline were found to suppress the spontaneous in vitro IgE synthesis of peripheral blood mononuclear cells (MNC) from patients with atopic dermatitis, when added at high concentrations (10(-3) -10(-4) M) to the IgE-producing cell cultures. In contrast, low concentrations of the substances (10(-8) -10(-12) M) significantly enhanced IgE production. This enhancement was probably due to effects of cAMP on T cells since pretreatment of allogeneic MNC or T cells with dbcAMP abrogated their suppressive effect or resulted in enhancement of IgE synthesis in coculture experiments. Likewise, pretreated T cells from atopics stimulated the IgE production of autologous B cells more than did untreated T cells. These findings may possibly have bearing on the pathogenesis of the atopic diseases, which are associated with abnormalities of the cyclic nucleotide metabolism.