Postelicitation model of allergic contact dermatitis for predicting the efficacy of topical drugs

Abstract

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.

Anti-Inflammatory Effects of Urocanic Acid Derivatives in Models Ex Vivo and In Vivo of Inflammatory Bowel Disease

“…The absorption of UV-radiation by this compound leads to a partial isomerisation to cis -UCA, or to (photo) oxidation yielding UCA oxidation products [13]. Both have shown to have anti-inflammatory effects both in vivo and in vitro [14–16]. In the case of cis -UCA, attenuation of experimental colonic epithelial damage, induced by dextran sodium sulfate (DSS), has recently been obtained in vivo [17].…”

“…Several UCA derivatives are potential anti-inflammatory agents, primarily developed for topical applications on inflamed skin [15, 16]. …”

In vitro and in vivo analysis of pro‐ and anti‐inflammatory effects of weak and strong contact allergens

“…Pretreatment of the skin with SLs prior to sensitization with TNCB suppresses CHS efficiently. The CHS model may therefore be useful to assess the efficiency of topical drugs for treatment of ACD in the prevention of sensitization and elicitation of CHS (28). Further studies have to demonstrate whether even elicitation of CHS can be reduced by drugs, such as Arnica preparations.…”

Extended DNFB‐induced contact hypersensitivity models display characteristics of chronic inflammatory dermatoses

“…Dermal sensitizers like 2,4,6‐trinitrochlorobenzene (TNCB), oxazolone or 2,4‐dinitrofluorobenzene (DNFB) are commonly used to stimulate an acute CHS, which exhibits a T‐cell‐dependent inflammatory response to cutaneous sensitization and subsequent challenges. A variety of CHS models have been established using different sensitizers, sensitization/challenge schedules and mouse strains (14,15). The dermal sensitizer DNFB is commonly used to evoke a type 1 cytokine‐dominated skin inflammation in C57BL/6 mice (16).…”