Postelicitation model of allergic contact dermatitis for predicting the efficacy of topical drugs.
To evaluate the anti-inflammatory efficacies of topical drugs, models of contact hypersensitivity (CHS) can be used, but the conventional murine models of CHS need revision in this respect. These models utilize sensitized mice to study suppression of sensitization or elicitation by test compounds. To mimick the events occurring in allergic contact dermatitis (ACD), a modification of the murine model of CHS is needed in a way that a chronic postelicitation phase of CHS is maintained for studies of anti-inflammatory effects of topical drugs, typically relevant for ACD therapy, not for ACD prevention. A method for the quantification of the suppression of ACD by a test compound is presented here. Two experimental drugs for topical use, imidazole-4-carboxylate and imidazole-4-acetate, were tested in parallel with the corticosteroid prednisolone. We found that prednisolone showed strong suppressive effects, while imidazole-4-carboxylate and imidazole-4-acetate showed mild suppressive effects during persistent ACD simulation. Multiple elicitations on the mouse ears led to scratching and the formation of abrasions and scabbings with, presumably, worsening of discomfort. Clear reduction of these side-phenomena was achieved by tailoring the topical amount of contact sensitizer, while the ability of the ACD model to test anti-inflammatory compounds, was not affected. By focussing on a prolonged postelicitation phase of CHS, a simulation of ACD has been established. We demonstrated that this model may provide an improved predictability for the clinical efficacies of (experimental) mild or strong anti-inflammatory drugs.
Kammeyer
Arthur
A
Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.kammeyer@amc.uva.nl
Bos
Jan D
JD
Teunissen
Marcel B M
MB
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation; D051379:Mice; D008807:Mice, Inbred BALB C
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D002264:Carboxylic Acids; D007093:Imidazoles; C029899:imidazole