title: The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes.
abstract: Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-α, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-α, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment. Accordingly, EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-α production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-α and IL-10 and caused an IL-6 dominant response during second stimulation with viral or bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells.
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, University Hospital Charité, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Witte
authors.affiliation: Preclinical Research, Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany.
authors.forename: Egon
authors.initials: E
authors.lastname: Koch
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies, University Hospital Charité, Berlin, Germany; Institute of Medical Immunology, University Hospital Charité, Berlin, Germany.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany; Research Center Immunosciences, University Hospital Charité, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
mesh_terms: D016207:Cytokines / Q000276:immunology*; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D031316:Pelargonium / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D016207:Cytokines; D010936:Plant Extracts; D048049:Extracellular Signal-Regulated MAP Kinases