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Morphologic and Immunohistochemical Features of Experimentally Induced Allergic Contact Dermatitis in Göttingen Minipigs

Novartis Forschungsinstitut, Vienna, Austria

Many preclinical studies in investigative dermatology are performed preferably in pigs because pig skin is more similar to human skin than is rodent skin. A frequently used model is allergic contact dermatitis (ACD); however, this T-cell–mediated skin condition so far is not well characterized in pigs. The present study is aimed at the evaluation of morphologic and immunohistochemical features of experimentally induced acute ACD in Göttingen minipigs using 2,4-dinitrofluorobenzene (DNFB) as a hapten. Eight minipigs were sensitized with 10% DNFB and challenged 2 weeks later at different sites with 1% DNFB. In addition to clinical examinations, cutaneous blood flow was quantified by laser Doppler velocimetry (Periflux PF3). These examinations were performed before challenge and 8, 24, 48, and 72 hours after challenge. Skin biopsies were taken at the same time points, fixed, sectioned, and stained with Giemsa for histologic evaluation, or with mouse anti-swine monoclonal antibodies (CD1, CD2, CD4, CD5, CD8, CD25, CD45, MHCII) and with one mouse anti-human monoclonal antibody (CD62E) cross-reacting with swine for immunohistochemical evaluation. Positively stained cells were counted per square millimeter of epidermis and dermis by using a video image analyzing system (Videoplan Kontron). Erythema and cutaneous blood flow peaked at 24 hours. The major epidermal changes most pronounced at 48 hours were acanthosis, spongiosis, intracellular edema, exocytosis, and abscesses mainly containing neutrophils and mononuclear cells (MNC). Perivascular infiltrates of MNC as well as neutrophils and eosinophils were the most significant dermal changes, with peak levels at 24–48 hours. In biopsies taken before challenge, CD1⁺ dendritic cells were found in similar numbers and locations as MHCII⁺ cells in the epidermis. In the epidermis the maximum CD1⁺ cell decrease occurred at 24 hours whereas in the dermis the maximum increase in CD1⁺ stained cells was seen at 72 hours. The dermal infiltrate (CD2⁺, CD5⁺, CD25⁺, and CD45⁺) was most dense at 48 hours. Between 8 and 48 hours more CD4⁺ were present than CD8⁺ cells, whereas at 72 hours CD4⁺ and CD8⁺ cells were similar in numbers. These findings closely resemble changes in human ACD. Therefore, DNFB-induced ACD in Göttingen minipigs is considered to be an appropriate animal model to study immunopathologic mechanisms and pharmacologic intervention.

Key words: Allergic contact dermatitis; 2,4-dinitrofluorobenzene; Göttingen minipig; histopathology; immunohistochemistry; skin inflammation; swine.

Requests reprints from Dr. J. G. Meingassner, Novartis Forschungsinstitut, Brunnerstrasse 59, A 1235 Vienna (Austria).

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