Direct effects of second-generation H1-receptor antagonists on the activation of human basophils

Abstract

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.

Histamine

“…Since then, both first-and second-generation compounds have been found to demonstrate a wide variety of effects not attributable to H 1 -receptor binding; Table III summarizes some of these effects studied for basophils and mast cells. [31][32][33][34][35][36][37][38][39][40][41][42] The list would be much longer if effects on other cell types were considered. In general, however, inhibition of cellular functions occurs at antihistamine concentrations that are significantly higher than their ability to saturate H 1 -receptors and outside the therapeutic range (typical inhibitory concentration of 50% values, 10 to 50 µmol/L).…”

Beyond the histamine receptor: effect of antihistamines on mast cells

“…Ramachers et al . compared the effects of several second‐generation antihistamines on mediator release from basophil and showed that terfenadine was the most effective at attenuating histamine release following both antigen and anti‐IgE‐induced activation [ 6]. The authors also note that attenuation of LTC 4 production was apparent for oxatomide, loratadine and terfenadine.…”

“…Different experimental conditions, different stimuli (immunological and non-immunological) and the known heterogeneity of response of mast cells [4] may explain some of the variability observed. Ramachers et al compared the effects of several second-generation antihistamines on mediator release from basophil and showed that terfenadine was the most effective at attenuating histamine release following both antigen and anti-IgE-induced activation [6]. The authors also note that attenuation of LTC 4 production was apparent for oxatomide, loratadine and terfenadine.…”

“…Antigen, administered under experimental conditions to the skin, nose, lungs or eyes of atopic humans, will induce [19] Human lung Histamine/PGD 2 /LTC 4 /D 4 Fabre et al 1995 [11] Human lung PGD 2 /LTC 4 /D 4 Human colon Ϯ PGD 2/ Ϯ LTC4/D4 Nabe et al 1989 [20] Basophils Histamine Ramachers et al 1994 [6] Basophils Histamine/LTC 4 allergic inflammation at that site. Mast cell mediators are released into various bodily fluids (e.g.…”

Local antihistamines

“…However, comparative studies between antihistamines suggest that these properties do not have a major infiuence on clinical benefit. Attenuation of histamine and leukotriene C4 release from basophils, mast cells and neutrophils has been demonstrated in vitro for many second-generation antihistamines, including terfenadine, loratadine and to a lesser extent cetirizine and astemizole [22,23]. Azelastine has also been shown to have this effect [24].…”