title: Anti-inflammatory and immune-regulatory mechanisms prevent contact hypersensitivity to Arnica montana L.
abstract: Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)-kappaB activation because of alkylation of the p65 subunit. Despite its known immunosuppressive action, Arnica has been classified as a plant with strong potency to induce allergic contact dermatitis. Here we examined the dual role of SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We tested the anti-inflammatory and allergenic potential of SL in the mouse contact hypersensitivity model. We also used dendritic cells to study the activation of NF-kappaB and the secretion of interleukin (IL)-12 in the presence of different doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-kappaB activation and IL-12 production in dendritic cells at high concentrations, but had immunostimulatory effects at low concentrations. Contact hypersensitivity could not be induced in the mouse model, even when Arnica tinctures or SL were applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene and activation of dendritic cells. However, contact hypersensitivity to Arnica tincture could be induced in acutely CD4-depleted MHC II knockout mice. These results suggest that induction of contact hypersensitivity by Arnica is prevented by its anti-inflammatory effect and immunosuppression as a result of immune regulation in immunocompetent mice.
authors.affiliation: Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Lass
authors.forename: Marc
authors.initials: M
authors.lastname: Vocanson
authors.forename: Steffen
authors.initials: S
authors.lastname: Wagner
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Schempp
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Nicolas
authors.forename: Irmgard
authors.initials: I
authors.lastname: Merfort
authors.forename: Stefan F
authors.initials: SF
authors.lastname: Martin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D018650:Arnica; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007509:Irritants / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008519:Medicine, Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D012717:Sesquiterpenes / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D007509:Irritants; D007783:Lactones; D008024:Ligands; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D012717:Sesquiterpenes; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4