title: Selective increase of cerebrospinal fluid IL-6 during experimental systemic inflammation in humans: association with depressive symptoms.
abstract: Systemic inflammation is accompanied by profound behavioral and mood changes that resemble symptoms of depression. Findings in animals suggest that pro-inflammatory cytokines released by activated immune cells in the periphery evoke these behavioral symptoms by driving inflammatory changes in the brain. However, experimental data in humans are lacking. Here we demonstrate in healthy male volunteers (10 endotoxin treated, 8 placebo treated) that intravenous administration of low-dose endotoxin (0.8 ng/kg body weight), a prototypical pathogen-associated molecular pattern that activates the innate immune system, not only induces a significant increase in peripheral blood cytokine concentrations (that is, tumor necrosis factor-α, interleukin (IL)-6, IL-10) but also results, with some latency, in a robust and selective increase of IL-6 in the cerebrospinal fluid (CSF). Moreover, we found a strong association between the endotoxin-induced increase of IL-6 in the CSF and the severity of mood impairment, with larger increases in CSF IL-6 concentration followed by a greater deterioration in mood. Taken together, these findings suggest that the appearance of depressive symptoms in inflammatory conditions might be primarily linked to an increase in central IL-6 concentration, identifying IL-6 as a potential therapeutic target in mood disorders.
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Engler
authors.affiliation: Clinic for Anesthesiology and Intensive Care Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Brendt
authors.affiliation: Clinic for Anesthesiology and Intensive Care Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Wischermann
authors.affiliation: Department of Orthopedic and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wegner
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Röhling
authors.affiliation: Department of Neurosurgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schoemberg
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Meyer
authors.affiliation: Department of Neurology, St Josef-Hospital, Ruhr University, Bochum, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Gold
authors.affiliation: Clinic for Anesthesiology and Intensive Care Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Peters
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: S
authors.identifier: 0000-0002-4487-4258
authors.initials: S
authors.lastname: Benson
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schedlowski
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood; D003863:Depression / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000378:metabolism; D004731:Endotoxins / Q000008:administration & dosage*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000523:psychology; D015850:Interleukin-6 / Q000134:cerebrospinal fluid* / Q000276:immunology; D008297:Male; D055815:Young Adult
chemical_list: D016207:Cytokines; D004731:Endotoxins; C508600:IL6 protein, human; D015850:Interleukin-6