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Selective increase of cerebrospinal fluid IL-6 during experimental systemic inflammation in humans: association with depressive symptoms

Molecular Psychiatry volume 22, pages 1448–1454 (2017)Cite this article

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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.

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Acknowledgements

We thank Ursula Brecklinghaus and Alexandra Kornowski for excellent technical assistance and Bettina Löschner and Dr Ingo Spreitzer (Paul-Ehrlich-Institute, Langen, Germany) for endotoxin safety testing. This work was supported by an internal research grant from the Medical Faculty of the University of Duisburg-Essen (IFORES) awarded to HE.

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Authors and Affiliations

  1. Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    H Engler, R Röhling, S Benson & M Schedlowski

  2. Clinic for Anesthesiology and Intensive Care Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    P Brendt, J Wischermann & J Peters

  3. Department of Orthopedic and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    A Wegner

  4. Department of Neurosurgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    T Schoemberg

  5. Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland

    U Meyer

  6. Department of Neurology, St Josef-Hospital, Ruhr University, Bochum, Germany

    R Gold

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  1. H Engler
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Engler, H., Brendt, P., Wischermann, J. et al. Selective increase of cerebrospinal fluid IL-6 during experimental systemic inflammation in humans: association with depressive symptoms. Mol Psychiatry 22, 1448–1454 (2017). https://doi.org/10.1038/mp.2016.264

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