Reproducible Biphasic Cutaneous Edema Induced by Topical and Repeated Application of Antigen in Sensitized Mice

An allergic dermatitis model was developed by repeated sensitization and challenge with antigen (ovalbumin, OA) over 7 months in mice. ddY mice were sensitized by i.p. injection of OA adsorbed in Al(OH)3 (1 μg OA/2 mg Al(OH)3/animal one every 3 weeks. Antigen challenge was conducted by injection of OA solution (0.1, 1 and 10 μg/site) into the skin of the hind paw instep 10 d after the respective sensitizations. At the 1st challenge, all the 3 groups showed an immediate edematous response with the peak at 30 min or 1 h after the challenge. The group challenged with the highest dose (10 μg/site) of the antigen developed a clear late-phase edema, which was observed at the 2nd challenge, increasing until the 3rd challenge, reaching a plateau at further challenges. On the other hand, such late phase edema scarcely developed in the group challenged with the lowest dose (0.1 μg/site) of the antigen. The amount of circulating specific IgE antibody increased following repeated sensitizations and challenges in all groups, but there were no significant differences in the levels among them. Mepyramine suppressed the early edema by approximately 50%, yet the late phase edema was unaffected. In conclusion, using Al(OH)3+antigen for sensitization and an appropriate amount of antigen for challenge, reproducible biphasic edematous responses were observed long-term without desensitization. This model may by classified as an acute allergic dermatitis and can be useful for quantitatively evaluating the effects of anti-allergic drugs.