Clinical and translational science · 2018
Comprehensive, Multimodal Characterization of an Imiquimod-Induced Human Skin Inflammation Model for Drug Development.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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van der Kolk Tessa, Assil Salma, Rijneveld Rianne, Klaassen Erica S, Feiss Gary, Florencia Edwin, Prens Errol P, Burggraaf Jacobus, Moerland Matthijs, Rissmann Robert, van Doorn Martijn B A
Аннотация
Imiquimod (IMQ) is often used as a topical challenge agent to provoke local skin inflammation. The objective of this study was to develop and refine a rapid, temporary, and reversible human skin inflammation model with IMQ for application in clinical drug development. A randomized, vehicle-controlled, open-label, dose-ranging study was conducted in 16 healthy male subjects. IMQ (5 mg) was applied once daily for 72 hours under occlusion to intact skin (n = 8) or tape stripped (TS) skin (n = 8). Although IMQ alone induced limited effects, TS+IMQ treatment showed larger responses in several domains, including erythema and perfusion (P < 0.0001), mRNA expression of inflammatory markers (P < 0.01), and inflammatory cell influx compared with vehicle. In conclusion, a rapid, human IMQ skin inflammation challenge model was successfully developed with a clear benefit of TS prior to IMQ application. Future interaction studies will enable proof-of-pharmacology of novel compounds targeting the innate immune system.