title: Extended DNFB-induced contact hypersensitivity models display characteristics of chronic inflammatory dermatoses.
abstract: Despite recent developments, there is a high medical need for new treatment options for chronic inflammatory dermatoses like allergic contact dermatitis (ACD) and psoriasis. Particularly, more predictive skin inflammation models are required to facilitate the process of drug discovery. Murine contact hypersensitivity (CHS) models adequately reflect ACD and are also used to characterize therapeutic approaches for psoriasis. Using the hapten 2,4-dinitrofluorobenzene (DNFB), we established new subacute and subchronic DNFB-induced CHS models in C57BL/6 mice, which more closely reflect the characteristics of chronic T-cell-dependent inflammatory dermatoses as pronounced keratinocyte proliferation, strong hypervascularization, immune cell infiltration and overexpression of T cell and inflammatory cytokines. For the subacute DNFB model, we demonstrated anti-inflammatory activity of the glucocorticoid, prednisolone, as well as of neutralization of TNFα, IL-12/IL-23 or IL-18. In the subchronic DNFB-induced CHS model, deficiency for MyD88 and IL-12/IL-35 p35 chain but not IL-12/IL-23 p40 chain led to decreased skin inflammation. Furthermore, as exemplified by the dose-dependently effective therapeutic prednisolone treatment, the subchronic model allows the continuous therapy of a pre-established stable contact dermatitis. Altogether, prolonged DNFB-induced mouse CHS models closely reflect ACD sensitive to glucocorticoids as standard therapy, reveal a more chronic skin inflammation and are responsive to cytokine antagonization.
authors.affiliation: Immunotherapy & Antibody-Drug Conjugates, Bayer Pharma AG, Berlin, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Röse
authors.forename: Claudia
authors.initials: C
authors.lastname: Schneider
authors.forename: Christine
authors.initials: C
authors.lastname: Stock
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Zollner
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Döcke
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002908:Chronic Disease; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy / Q000209:etiology*; D004139:Dinitrofluorobenzene / Q000633:toxicity*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011239:Prednisolone / Q000627:therapeutic use; D011565:Psoriasis / Q000209:etiology
chemical_list: D000893:Anti-Inflammatory Agents; D011239:Prednisolone; D004139:Dinitrofluorobenzene