Effect of H1-antihistamines on histamine release from dispersed canine cutaneous mast cells

Abstract

Listen

Translate article

Abstract Objective Because of the implication of histamine in canine atopic dermatitis, H1-antihistamines may provide a valid alternative to glucocorticoid therapy. In vitro study of these drugs prior to clinical testing can allow the most promising compounds to be selected for trials and render trials with drugs of doubtful efficacy unnecessary. Sample Population Isolated canine cutaneous mast cells. Procedure Cells were preincubated with antihistamines at increasing concentrations and incubated with concanavalin A (1,000 µg/ml), calcium ionophore A23187 (1 µM), and substance P (100 µM). Compound 48/80 was not used because it proved to be cytotoxic. Results Generally, significant prodegranulating effect was not observed for most of the studied agents. Only terfenadine increased spontaneous histamine release at concentrations > 30 µM. Cetirizine did not block histamine release at any of the studied concentrations. Ketotifen had a low inhibitory effect only at the highest concentration (100 µM) after concanavalin A- (23.6 ± 2.8%) and calcium ionophore A23187- (29.8 ± 3.0%) induced release. Terfenadine caused a concentration-dependent inhibitory effect after ionophore A23187- (48.1 ± 2.2%) and concanavalin A- (28.9 ± 2.3%) activation, but was inactive against substance P-induced release. In contrast, loratadine had potent dose-dependent inhibition of concanavalin A- and ionophore A23187-induced histamine release, with maximal effect of 85.6 ± 3.1 % and 62.6 ± 4.7%, respectively, at 100 µM concentration. After substance P activation, histamine release was only slightly inhibited by loratadine (14.8 ± 1.1%). Conclusions This study documents the behavior of isolated canine cutaneous mast cells in the presence of nonimmunologic stimulation. Using this in vitro method, we were able to determine that loratadine is the only antihistamine that has potent inhibition of histamine release from dog cutaneous mast cells without a substantial prodegranulating effect. Loratadine is, therefore, a good candidate for clinical testing. (Am J Vet Res 1997;58:293–297)