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


CONCLUSIONS
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.
Sato
Eiichiro
E
Research Laboratories, Sankyo Co, Ltd, Tokyo, Japan.
Hirahara
Kazuki
K
Wada
Yoshihiro
Y
Yoshitomi
Tomomi
T
Azuma
Takachika
T
Matsuoka
Kunie
K
Kubo
Shuichi
S
Taya
Choji
C
Yonekawa
Hiromichi
H
Karasuyama
Hajime
H
Shiraishi
Akio
A
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D003872:Dermatitis / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004423:Ear; D004487:Edema / Q000276:immunology; D000939:Epitopes; D006241:Haptens / Q000008:administration & dosage; D007073:Immunoglobulin E / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D010851:Picrates / Q000276:immunology
D000941:Antigens; D000939:Epitopes; D006241:Haptens; D010851:Picrates; D007073:Immunoglobulin E; C005858:picric acid