title: Induction of pro-inflammatory cytokine production in thymocytes by the immune response modifiers Imiquimod and Gardiquimod™.
abstract: An emerging role is postulated for IL-17-producing thymocytes, which in their majority consist of IL-17-producing CD4(+) cells. For these, a specific role in the immediate defense against infectious pathogens is suggested, independent from the development of an adaptive immune response in the immune periphery. Immune response modifiers, like the TLR7 ligands Imiquimod and Gardiquimod™ are effective pharmacological therapeutics applied topically against dermal tumors and virus infections and have been demonstrated to activate immune cells. In this study, we investigated the effect of Imiquimod and Gardiquimod™ on murine thymocyte cytokine production with a particular focus on IL-17. We find that both substances dose-dependently are able to trigger IFN-γ and IL-6 production, but no IL-17 production. Moreover, a strong co-stimulating effect is detected on α-CD3-induced IFN-γ, IL-6 and IL-17 production. We conclude that Imiquimod and Gardiquimod™ are not only modifiers of the adaptive immune response, but might also have additional therapeutic potential by modifying the immune activity in the thymus.
authors.affiliation: Department of Neurology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weber
authors.forename: Corinna
authors.initials: C
authors.lastname: Zimmermann
authors.forename: Anne K
authors.initials: AK
authors.lastname: Mausberg
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Harald H
authors.initials: HH
authors.lastname: Hofstetter
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D000077271:Imiquimod; D007239:Infections / Q000276:immunology / Q000628:therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D060168:Thymocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007093:Imidazoles; D018836:Inflammation Mediators; D015850:Interleukin-6; C546771:gardiquimod; D007371:Interferon-gamma; D000077271:Imiquimod
keywords: Cytokine; Immune response modifier; Interleukin 17; T cell; Thymus