title: Immune dysregulation in flea allergy dermatitis--a model for the immunopathogenesis of allergic dermatitis.
abstract: BACKGROUND
  Flea allergy dermatitis (FAD) is a common skin disease in dogs and can be induced experimentally. It often coexists with other allergic conditions. So far no studies have investigated the quantitative production of cytokine mRNA in skin biopsies and peripheral blood mononuclear cells (PBMC) in flea allergic dogs.
  
  
  OBJECTIVE
  The aim of our study was to improve the understanding of the immunopathogenesis of allergic dermatitis as a response to fleabites.
  
  
  METHODS
  Allergic and non-allergic dogs were exposed to fleas. Before and after 4 days of flea exposure mRNA was isolated from biopsies and PBMC. Production of chymase, tryptase, IL-4, IL-5, IL-13, TNF-alpha and IFN-gamma mRNA was measured by real-time RT-PCR. The inflammatory infiltrate in the skin was scored semi-quantitatively. The number of eosinophils, mast cells (MC) and IgE+ cells/mm2 was evaluated to complete the picture.
  
  
  RESULTS
  FAD was associated with a higher number of MC before flea exposure and with a significant increase of eosinophils after flea exposure as compared to non-allergic dogs. The number of IgE+ cells was higher in allergic dogs before and after flea exposure. In allergic dogs mRNA for most cytokines and proteases tested was higher before flea exposure than after flea exposure. After exposure to fleas an increased mRNA production was only observed in non-allergic dogs. In vitro stimulation with flea antigen resulted in a decreased expression of most cytokines in allergic dogs before flea exposure. In contrast, in PBMC, only increased levels of IL-4 and IL-5 mRNA were observed in allergic dogs before flea exposure. However, after flea exposure and additional stimulation with flea antigen the production of mRNA for all cytokines tested was significantly increased in allergic dogs.
  
  
  CONCLUSIONS
  We demonstrated that the response in biopsies and PBMC is different and that FAD is associated with a TH2 response.
authors.affiliation: Institute of Animal Pathology, Vetsuisse Faculty, University of Berne, Postfach, Länggassstrasse 122, CH-3001 Berne, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Wuersch
authors.forename: C
authors.initials: C
authors.lastname: Brachelente
authors.forename: M
authors.initials: M
authors.lastname: Doherr
authors.forename: M
authors.initials: M
authors.lastname: Reist
authors.forename: U
authors.initials: U
authors.lastname: Sattler
authors.forename: U
authors.initials: U
authors.lastname: Forster
authors.forename: G
authors.initials: G
authors.lastname: Bertoni
authors.forename: J E
authors.initials: JE
authors.lastname: Peel
authors.forename: M
authors.initials: M
authors.lastname: Welle
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003872:Dermatitis / Q000276:immunology* / Q000503:physiopathology / Q000662:veterinary*; D004283:Dog Diseases / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D004285:Dogs; D004478:Ectoparasitic Infestations / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000662:veterinary*; D005786:Gene Expression Regulation / Q000276:immunology; D007073:Immunoglobulin E / Q000378:metabolism; D007249:Inflammation / Q000662:veterinary; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008407:Mast Cells; D010447:Peptide Hydrolases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D005423:Siphonaptera / Q000276:immunology*; D012882:Skin Tests / Q000662:veterinary
chemical_list: D000941:Antigens; D016207:Cytokines; D012333:RNA, Messenger; D007073:Immunoglobulin E; D010447:Peptide Hydrolases