Development of an ear edema model of contact hypersensitivity to avoid false-positive results due to interactions between hapten and test agents.
Ear edema models are regularly used for topical testing of antiinflammatory compounds. However, test compounds are usually applied simultaneously with proinflammatory agents at the same site which may result in mutual interactions. In order to avoid the occurrence of false antiinflammatory effects, a model of oxazolone-induced contact hypersensitivity has been described in which the hapten and test compound are each applied separately to only one side of the ear. By splitting and weighing the dorsal and ventral cutis of the ears, it was shown that the edemateous response of the control nonhapten side was comparable with the hapten-treated side. Some agents with antiinflammatory properties, as for example, dapsone, cimetidine, cyclosporine A, and budesonide, were tested simultaneously with oxazolone on both sides of the ear or applied separately on the dorsal and ventral ear sides, respectively. When dissolving the compounds in solutions of oxazolone, marked colorations of the test solutions were noted, indicating the occurrence of a chemical interaction. On simultaneous application at the same area, almost complete inhibition of the edemateous response was obtained for all compounds tested. In contrast, when applied separately, only budesonide appeared to exhibit antiinflammatory activity. The results indicate that the proposed model can be used to avoid the occurrence of interactions between oxazolone, and possibly other sensitizers, and substances that are being evaluated for topical antiinflammatory activity. By use of this model spurious antiinflammatory activity can be detected.
van den Hoven
W E
WE
Pharmacology Department, Yamanouchi Research Laboratories, Yamanouchi Europe B.V., AC Leiderdorp, The Netherlands.
van den Berg
T P
TP
Hall
D W
DW
van der Goot
H
H
Timmerman
H
H
D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000818:Animals; D016477:Artifacts; D019819:Budesonide / Q000633:toxicity; D003877:Dermatitis, Contact / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004347:Drug Interactions / Q000276:immunology; D004423:Ear / Q000473:pathology*; D004487:Edema / Q000139:chemically induced* / Q000473:pathology; D005189:False Positive Reactions; D005260:Female; D006241:Haptens / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D010081:Oxazolone / Q000633:toxicity*; D018675:Toxicity Tests
D000276:Adjuvants, Immunologic; D006241:Haptens; D010081:Oxazolone; D019819:Budesonide