Chronic inflammation of the skin can be induced in IgE transgenic mice by means of a single challenge of multivalent antigen

Abstract

Background: It is now widely accepted that IgE mediates immediate-type allergic response. However, the pathologic role of IgE is controversial in the chronic allergic inflammation observed in atopic diseases, such as asthma and atopic dermatitis. Objective: We investigated the role of IgE in cutaneous allergic reactions by using 2 newly developed lines of antigen-specific IgE transgenic mice. Methods: IgE transgenic mice were administered subcutaneously with corresponding antigens, and the subsequent ear swelling was measured. Results: A single subcutaneous administration of TNP-conjugated ovalbumin (OVA) into the ears of nonimmunized mice carrying the TNP-specific IgE transgene elicited immediate-phase and late-phase ear swelling as expected, which peaked at 20 minutes and 8 hours later, respectively. Interestingly, however, 2 to 3 days after the antigen challenge, more intense ear swelling appeared. Its magnitude and duration were dependent on the valency of TNP in OVA, as well as the dose of TNP-OVA, and it lasted over 1 month when 100 μg of OVA conjugated with 11 molecules of TNP was given. Interestingly, administration of OVA to OVA-specific IgE transgenic mice elicited immediate-phase and late-phase ear swelling but not third-phase ear swelling. Massive infiltration of inflammatory cells was observed in the third-phase ear swelling of TNP-specific IgE transgenic mice. Cyclosporine A almost completely inhibited the third-phase ear swelling and cellular infiltration, whereas an antihistamine, cyproheptadine, did not show any significant effect on the third-phase reaction. Conclusion: These results indicate that IgE can trigger not only immediate-type hypersensitivity but also chronic allergic inflammation. Our findings highlight a novel immunopathologic role of IgE in chronic atopic disorders. (J Allergy Clin Immunol 2003;111:143-8.)