T J Nuttall1, P A Knight, S M McAleese, J R Lamb, P B Hill. 1. University of Edinburgh Department of Veterinary Clinical Science, Hospital for Small Animals, Easter Bush Veterinary Centre, Midlothian, UK. timn@liv.ac.uk
Abstract
BACKGROUND: Atopic dermatitis is a common inflammatory skin disease of humans and dogs. Human atopic dermatitis is associated with Th2-type responses, although Th1 cytokines can be identified in chronic lesions. In contrast, tolerance to environmental allergens in healthy individuals is mediated by regulatory T cells. OBJECTIVE: This study examined the expression of the immunosuppressive cytokines TGF-beta and IL-10, the Th2-type cytokines IL-4 and IL-6, and the Th1-type cytokines IFN-gamma, TNF-alpha, IL-2, IL-12p35 and IL-12p40, in canine atopic dermatitis. MATERIALS AND METHODS: RNA was isolated from lesional atopic, non-lesional atopic and healthy canine skin samples. Semi-quantitative reverse transcriptase polymerase chain reactions (RT-PCRs) were carried out using specific primers and one-way analyses of variance used to compare cytokine expression in each group. RESULTS: Canine atopic dermatitis was associated with over-expression of IL-4 mRNA and reduced transcription of TGF-beta compared with healthy skin (P < 0.05). Higher levels of IFN-gamma, TNF-alpha and IL-2 mRNA were seen in lesional compared with non-lesional and healthy skin (P < 0.05). There were no significant differences in IL-10, IL-6, IL-12p35 or IL-12p40 transcription between the three groups. CONCLUSIONS: This is the first report to demonstrate that canine atopic dermatitis is associated with over-production of IL-4. Clinical tolerance in healthy individuals appears to be associated with TGF-beta, although it is unclear if this reflects an active mechanism or simply non-responsiveness of the immune system. Th1 cytokines may be induced by subsequent self-trauma and secondary infections in atopic skin. We believe that these results better characterize spontaneously occurring canine atopic dermatitis. We further propose that this should be investigated as a possible animal model of human atopic dermatitis.
BACKGROUND:Atopic dermatitis is a common inflammatory skin disease of humans and dogs. Humanatopic dermatitis is associated with Th2-type responses, although Th1 cytokines can be identified in chronic lesions. In contrast, tolerance to environmental allergens in healthy individuals is mediated by regulatory T cells. OBJECTIVE: This study examined the expression of the immunosuppressive cytokines TGF-beta and IL-10, the Th2-type cytokines IL-4 and IL-6, and the Th1-type cytokines IFN-gamma, TNF-alpha, IL-2, IL-12p35 and IL-12p40, in canineatopic dermatitis. MATERIALS AND METHODS: RNA was isolated from lesional atopic, non-lesional atopic and healthy canine skin samples. Semi-quantitative reverse transcriptase polymerase chain reactions (RT-PCRs) were carried out using specific primers and one-way analyses of variance used to compare cytokine expression in each group. RESULTS:Canineatopic dermatitis was associated with over-expression of IL-4 mRNA and reduced transcription of TGF-beta compared with healthy skin (P < 0.05). Higher levels of IFN-gamma, TNF-alpha and IL-2 mRNA were seen in lesional compared with non-lesional and healthy skin (P < 0.05). There were no significant differences in IL-10, IL-6, IL-12p35 or IL-12p40 transcription between the three groups. CONCLUSIONS: This is the first report to demonstrate that canineatopic dermatitis is associated with over-production of IL-4. Clinical tolerance in healthy individuals appears to be associated with TGF-beta, although it is unclear if this reflects an active mechanism or simply non-responsiveness of the immune system. Th1 cytokines may be induced by subsequent self-trauma and secondary infections in atopic skin. We believe that these results better characterize spontaneously occurring canineatopic dermatitis. We further propose that this should be investigated as a possible animal model of humanatopic dermatitis.
Authors: Shona Hiedi Wood; Xiayi Ke; Tim Nuttall; Neil McEwan; William E Ollier; Stuart D Carter Journal: Immunogenetics Date: 2010-01-05 Impact factor: 2.846
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