title: Oxymetazoline modulates proinflammatory cytokines and the T-cell stimulatory capacity of dendritic cells.
abstract: The nasal decongestant oxymetazoline (OMZ) is frequently used in the topical treatment of rhinitis/sinusitis. As proinflammatory cytokines play a critical role in the development and maintenance of local inflammation, the aim of this study was to investigate the influence of OMZ on immune cells in order to diminish the mucosal infiltration of the nose. Peripheral blood mononuclear cells (PBMC) from buffy coats of healthy volunteers were isolated and stimulated in the presence or absence of OMZ. In addition, monocyte-derived dendritic cells (DC) were generated and different concentrations of OMZ were added. DC phenotype and their T-cell stimulatory properties were analysed. The vasoactive substance OMZ showed a concentration dependent inhibitory effect on T-cell activation as well as a dominant effect on T-cell stimulatory properties of DC. Low concentrations of OMZ inhibited the proliferation of polyclonally activated T cells. In addition, secretion of proinflammatory mediators such as the cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF alpha), IL-6 and IL-8 were inhibited in the presence of physiological doses of OMZ. Interestingly, the addition of IL-6 to DC-T-cell co-culture was able to completely restore T-cell proliferation. In conclusion, these findings indicate that the anti-inflammatory properties of OMZ are partially mediated by the inhibition of proinflammatory cytokines as well as reduced T-cell stimulatory capacity of DC resulting in a repressed stimulation of T cells. Therefore, the therapeutic benefit of OMZ can be explained in part by its immunomodulating effects in the topical treatment of nasal inflammation.
authors.affiliation: Department of Dermatology, University of Mainz, Mainz, Germany. tuettis@hotmail.com
authors.forename: Andrea
authors.initials: A
authors.lastname: Tuettenberg
authors.forename: Stephan
authors.initials: S
authors.lastname: Koelsch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Knop
authors.forename: Helmut
authors.initials: H
authors.lastname: Jonuleit
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D018189:Immunomagnetic Separation; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D014663:Nasal Decongestants / Q000494:pharmacology*; D010109:Oxymetazoline / Q000494:pharmacology*; D012220:Rhinitis / Q000188:drug therapy; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D016207:Cytokines; D014663:Nasal Decongestants; D010109:Oxymetazoline