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    Comparison of topical tofacitinib and 0.1% hypochlorous acid in a murine atopic dermatitis model (2018)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Fukuyama, Tomoki
    Ehling, Sarah
    Wilzopolski, Jenny (WE 14)
    Bäumer, Wolfgang (WE 14)
    Quelle
    BMC Pharmacology and Toxicology
    Bandzählung: 19
    Seiten: Artikelnr. 37
    ISSN: 2050-6511
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-018-0232-3
    DOI: 10.1186/s40360-018-0232-3
    Pubmed: 29970189
    Kontakt
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    +49 30 838 53221
    pharmakologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Topical administration of PR022, 0.05% hypochlorous acid (HOCl) in gel has been demonstrated to be beneficial in a chronic murine atopic dermatitis model. In a follow up study we tested a higher concentration (0.1%) of PR022 HOCl gel in comparison to the Janus kinase inhibitor tofacitinib, both of which are currently in clinical phase studies for treatment of human atopic dermatitis.

    The effect of topically administered HOCl (0.1%) in gel was compared to a topical formulation of tofacitinib (0.5%) in a therapeutic setting on atopic dermatitis-like lesions in NC/Nga mice as well as itch behaviour. NC/Nga mice were sensitized with house dust mite allergen. After reaching visible lesions, mice were treated either topically with HOCl or tofacitinib or gel vehicle for 17 days. After termination of the study, dorsal root ganglia were isolated for ex vivo stimulation and skin samples were taken for cytokine determination in inflamed skin.

    When administered onto lesional skin of NC/Nga mice, both HOCl and tofacitinib reduced lesions and scratching behaviour. The reduced inflammatory response by HOCl and tofacitinib treatment was demonstrated by diminished inflammatory cytokines in affected skin tissue from NC/Nga mice. Dorsal root ganglia neurons re-stimulated with a range of mediators of itch showed a reduced response compared to the vehicle control mice, when isolated from tofacitinib or HOCl treated mice.

    These data indicate a similar beneficial potential of topical high dose PR022 HOCl (0.1%) in gel and tofacitinib, in a translational murine model of atopic dermatitis.