Establishment of animal models for atopic dermatitis and induction of oral tolerance

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BALB/C mice were sensitized with 2,4,6-trinitro-chlorobenz ine, and then were repeatedly elicited on the original sensitized site with the same antigen at 2-day intervals for 24 days. To investigate the differences in the cutaneous cytokine milieu between the acute and chronic phases of contact hypersensitivity, sequential cytokine dynamics after 2,4,6-trinitro-chlorobenzine application were assessed in the acute vs chronic lesions, using RT-PCR technique. As a result, increased mRNA levels for Th1-type cytokines (IL-2, IFN-gamma) were observed in the acute lesions, whereas those for Th2-type cytokines (IL-4, IL-10) were markedly up-regulated in the chronic lesions.Similar study with BALB/C mice sensitized by subcutaneous nickel injection also showed that repeated applications of nickel gave rise to a shift from Th1 to Th2 dominated responses. Oral administration of nickel prior to repeated elicitation suppressed development of dermatitis. We demonstrated Th2-type responses in the repeatedly elicited sites, using RT-PCR technique.Subsequently, BALB/C mice were sensitized with 2,4,6-trinitro-chlorobenzine and then were repeatedly elicited on the original sensitized site with the same antigen at 2-day intervals for 24 days. Using in-situ hybridization technique, we examined time course and localization of expression for IFN-gamma mRNA and IL-10mRNA.In the acute lesions, we demonstrated increased expression for IFN-gamma mRNA on T cells in the dermis between several and 12 hours. Expression of IL-10mRNA on T cells in the dermis was up-regulated between 10 and 24 hours. In the chronic lesions, expression of IL-10mRNA was observed on infiltrating T cells into epidermis and dermis at 3-24 hours.