Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis.
Atopic dermatitis, a common, chronic, inflammatory skin disease that occurs with increasing prevalence, is characterized by hyperactivated cytokines of helper T cell subset 2 and is frequently associated with staphylococcal infection. An experimental animal model of atopic dermatitis induced by transgenically introduced cytokine is not available. We generated a transgenic mouse line expressing epidermal interleukin-4, a critical cytokine of helper T cell subset 2. Here we show that transgenic mice spontaneously developed a pruritic inflammatory skin disease reproducing all key features of human atopic dermatitis, including xerosis, conjunctivitis, inflammatory skin lesions, Staphylococcus aureus infection, histopathology of chronic dermatitis with T cell, mast cell, macrophage-like mononuclear cell, and eosinophil infiltration, and elevation of total serum IgE and IgG1. The onset and early progression of skin disease coincided with increased total serum IgE and IgG1. The mouse disease occurred at a 43% annual incidence rate and primarily affected the poorly haired skin: ear (100%), neck (65%), eye (53%), face (29%), tail (12%), leg (12%), and torso (6%). As a group the affected transgenic mice manifested with a skin disorder that fulfilled the clinical diagnostic criteria established for atopic dermatitis in human patients. Pending further characterization to authenticate it as a model of atopic dermatitis, this experimental animal model of pruritic inflammatory skin disease may facilitate investigations for the roles of interleukin-4 in cutaneous inflammation and skin infection in human patients.
Chan
L S
LS
Medicine Service, Lakeside Division, VA Chicago Health Care System, Chicago, Illinois, USA. larrychan@north-western.edu
Robinson
N
N
Xu
L
L
D000818:Animals; D015550:Cell Degranulation; D002908:Chronic Disease; D003876:Dermatitis, Atopic; D020405:Dermis / Q000473:pathology; D004195:Disease Models, Animal; D003875:Drug Eruptions / Q000097:blood / Q000382:microbiology / Q000473:pathology; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000473:pathology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009000:Monocytes / Q000473:pathology; D011537:Pruritus / Q000097:blood / Q000139:chemically induced* / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections; D013203:Staphylococcal Infections; D013601:T-Lymphocytes / Q000473:pathology
D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E