title: Inhibition of scratching behavior associated with allergic dermatitis in mice by tacrolimus, but not by dexamethasone.
abstract: Itching is the most important problem in many allergic and inflammatory skin diseases especially in atopic dermatitis. However, animal models for allergic dermatitis useful for the study of itching have rarely been established. We established a mouse allergic dermatitis model involving frequent scratching behavior by repeated painting with 2,4-dinitrofluorobenzene (DNFB) acetone solution onto the mouse skin, and comparatively examined the effects of tacrolimus and dexamethasone on the dermatitis and associated scratching behavior. Repeated DNFB painting caused typical dermatitis accompanied by elevated serum immunoglobulin E (IgE) and frequent scratching behavior. An apparent thickening of the epidermis and dermis, and the significant accumulation of inflammatory cells were observed. Increased interferon (IFN)-gamma mRNA expression and the induction of interleukin (IL)-4 and IL-5 mRNA expression were also observed in the skin lesion. The scratching behavior was inhibited by dibucaine and naloxone. Although tacrolimus reduced the increased expression of IFN-gamma and IL-4 mRNA, dexamethasone potently depressed that of IFN-gamma, IL-4 and IL-5 mRNA. Dexamethasone inhibited the accumulation of lymphocytes and eosinophils, although tacrolimus did not. Both drugs failed to inhibit the elevation of serum IgE levels. Tacrolimus significantly inhibited the scratching behavior that was associated with the inhibition of nerve fiber extension into the epidermis, whereas dexamethasone failed to have any effect. The mouse dermatitis model seems to be beneficial for the study of itching associated with allergic dermatitis, such as atopic dermatitis, and tacrolimus seems to exhibit an anti-itch effect through the inhibition of nerve fiber extension at least in part.
authors.affiliation: Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502-8585, Japan. inagakin@gifu-pu.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Inagaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Shiraishi
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Igeta
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Itoh
authors.forename: Takao
authors.initials: T
authors.lastname: Chikumoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nagao
authors.forename: John Fan
authors.initials: JF
authors.lastname: Kim
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Nagai
mesh_terms: D000485:Allergens / Q000276:immunology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000982:Antipruritics / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D003992:Dibucaine / Q000494:pharmacology; D004139:Dinitrofluorobenzene / Q000276:immunology; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011537:Pruritus / Q000517:prevention & control*; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000485:Allergens; D000779:Anesthetics, Local; D000982:Antipruritics; D005938:Glucocorticoids; D015848:Interleukin-5; D009292:Narcotic Antagonists; D012333:RNA, Messenger; D015847:Interleukin-4; D009270:Naloxone; D007073:Immunoglobulin E; D003907:Dexamethasone; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene; D003992:Dibucaine; D016559:Tacrolimus