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 antiinflamm atory compounds. However, test compounds are usually applied simultane ously with proinflammatory agents at the same site which may result in mutual interactions. In order to avoid the occurrence of false antiin flammatory effects, a model of oxazolone-induced contact hypersensitiv ity has been described in which the hapten and test compound are each applied separately to only one side of the ear. By splitting and weigh ing the dorsal and ventral cutis of the ears, it was shown that the ed emateous response of the control nonhapten side was comparable with th e hapten-treated side. Some agents with antiinflammatory properties, a s for example, dapsone, cimetidine, cyclosporine A, and budesonide, we re tested simultaneously with oxazolone on both sides of the ear or ap plied separately on the dorsal and ventral ear sides, respectively. Wh en dissolving the compounds in solutions of oxazolone, marked colorati ons of the test solutions were noted, indicating the occurrence of a c hemical interaction. On simultaneous application at the same area, alm ost complete inhibition of the edemateous response was obtained for al l compounds tested. In contrast, when applied separately, only budeson ide appeared to exhibit antiinflammatory activity. The results indicat e that the proposed model can be used to avoid the occurrence of inter actions between oxazolone, and possibly other sensitizers, and substan ces that are being evaluated for topical antiinflammatory activity. By use of this model spurious antiinflammatory activity can be detected. (C) 1997 Elsevier Science Inc.