The present study was performed to investigate the putative suppressive effects of H1-receptor antagonists (HRA) of the second generation (astemizole (AS), cetirizine (CT), loratadine (LO), oxatomide (OX) and terfenadine (TF)) on the mediator release from human basophils activated by two classical stimuli. Anti-IgE-mediated histamine release was inhibited in a dose-dependent fashion by TF (maximum inhibitory value: 33.8 +/- 7.6%, 100 microM, n = 7), whereas the other HRA exhibited weaker activity. The anti-IgE-induced LTC4 production was strongly suppressed by TF, LO and OX (92.4 +/- 6.3%, 90.8 +/- 6.0% and 88.5 +/- 5.6%, 100 microM, n = 4-5), while AS was less active (56.4 +/- 4.1%, 100 microM, n = 5). Histamine release induced by incubation with grass pollen antigen (0.01%) was inhibited by TF (40.7 +/- 4.1%, 50 microM, n = 4), but the other HRA showed only low activity. The present findings suggest that some HRA might exhibit direct inhibitory effects on activation of IgE-receptor bearing cells.

Protein kinase C (PKC) is suggested to be important for signal transduction of histamine-containing cells. The present study investigated the putative role of PKC in enhanced mediator release of basophils in atopic derm atitis (AD). Basophils were isolated from patients with severe AD (mean serum IgE level of 5,165 U/ml) and from healthy controls, and the effects of potent activators of PKC on histamine release were studied. The phorbol esters 12-o-tetradecanoyl-phorbol-13-acetate and phorbol-12,13-dibutyrate and the nonphorbol mezerein induced a dose-dependent mediator release, which was significantly lower in ‘atopic’ basophils at concentrations ≥1 μM. Recently, PKC levels have been shown to be lowered in atopic leukocytes compared to cells from healthy controls. The lowered response of PKC towards direct activation and lowered PKC levels may be due to high serum IgE levels and allergen exposure in vivo with subsequent down-regulation of different key elements of signal transduction.