Development of a Model of Dermal Inflammation and Irritation (Urticaria) in the Miniature Swine
Histamine, the major mediator of mast cells, is known to induce a short-lived urticaria when applied intradermally in humans. The objective of this study is to develop a reproducible dermal urticaria model in miniature swine. Three female Hanford miniature swine, age 3 to 18 months, were used in the study. The animals were pricked on their backs with a skin test device that was loaded with vehicle or histamine in vehicle. The irritation and wheal and flare responses of the dermis were evaluated with Draize scoring and with wheal size measurement. Histamine dose-dependently induced skin irritation at both 10 and 20 minutes post-treatment. The most prominent erythema and edema (Draize score) responses were observed at 10 minutes post-treatment; the responses were slightly diminished at 20 minutes post-treatment. Histamine also caused skin wheals that ranged between 4-7 mm in diameter. Although wheal sizes increased over time following treatment, this change in wheal size appeared unrelated to histamine effect. The optimal concentration of histamine to induce urticaria appeared to be 25 mg/mL. When urticaria was induced with 10 mg/mL histamine, topical antihistamine slightly inhibited both dermal irritation and wheal and flare, whereas topical hydrocortisone inhibited the wheal and flare only. When urticaria was induced with 25 and 50 mg/mL histamine, topical antihistamine as well topical hydrocortisone inhibited both dermal irritation and wheal and flare. The inhibitory effects of antihistamine and hydrocortisone were observed at 25 and 45 minutes post-dose. Histamine at 50 mg/mL was shown to induce urticaria with sustained dermal irritation and wheal and flare in Hanford miniature swine. In conclusion, a histamine-induced urticaria model has been established with the female Hanford miniature swine and can be used for the testing of topical treatments.
Zhong, M., Liu, J., Bouchard, G.F., Stricker-Krongrad, A.