Chronic mouse model of TMA-induced contact hypersensitivity.
Due to the steadily increasing incidence of atopic dermatitis (AD), especially in children, there is a high medical need for new therapies and improved animal models. In mice, trimellitic anhydride (TMA) is routinely used to trigger T-cell-dependent contact hypersensitivity (CHS) reactions. In this study, we compared the standard acute TMA-induced CHS in Balb/c mice with subacute and chronic models of TMA-induced ear inflammation. Compared to the acute model, the chronic CHS model more closely reflects characteristics of AD, such as typical morphological changes of the inflamed skin, strong infiltration with T cells, major histocompatibility complex II-positive cells, eosinophils, and mast cells, a T-helper cell-type (Th) 2 cytokine profile and a strong increase of serum IgE levels. Moreover, a strong lymph node involvement with T-helper cell dominance and a mixed Th1/Th2 T-cell differentiation and activation pattern was demonstrated. Importantly, as demonstrated by successful therapy with prednisolone, the chronic TMA-induced CHS model, in contrast to acute and subacute models, made prolonged therapeutic treatment of a pre-established skin inflammation possible. Altogether, we present an improved model of mouse T-cell-dependent skin inflammation for AD. We hope this model will enhance the predictive value of animal models for therapeutic treatment of atopic eczema.
Schneider
Claudia
C
TRG Inflammation and Immunology, Bayer Schering Pharma AG, Berlin, Germany.
Döcke
Wolf-Dietrich F
WD
Zollner
Thomas M
TM
Röse
Lars
L
D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010796:Phthalic Anhydrides / Q000633:toxicity*; D011239:Prednisolone / Q000627:therapeutic use; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D010796:Phthalic Anhydrides; D007073:Immunoglobulin E; C015559:trimellitic anhydride; D011239:Prednisolone