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Experimental Human Endotoxemia, Sickness Behavior, and Neuropsychiatric Diseases

  • Chapter
Immunology and Psychiatry

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 8))

Abstract

Systemic inflammation is among the most prominent and most frequently observed responses of the immune system. From everyday challenges like mild infections to severe forms such as chronic inflammatory diseases or sepsis, inflammatory states can develop in many ways over the lifespan. Over the past few decades, it has become clear that inflammatory events can have a strong impact on brain functions. Inflammatory mediators released by activated immune cells induce not only adaptive behavioral responses such as sickness behavior but also can lead to cognitive impairment and may even promote the development of mood disorders. Since most of these aspects cannot be sufficiently modeled in laboratory animals, there is a need for experimental inflammatory models in humans. Intravenous or intramuscular injection of bacterial lipopolysaccharide (LPS, endotoxin) represents a model to induce transient systemic low-grade inflammation in healthy human subjects. During the past two decades, this model has been increasingly used for psychoneuroimmunology (PNI) research. After a brief introduction into sickness behavior and the history of immune-to-brain research, we will summarize work employing this promising model beginning with the first studies on sleep alterations and ending with studies on social behavior using cutting-edge neuroimaging techniques like functional magnetic resonance imaging (fMRI) or positron emission tomography (PET). We will discuss potential difficulties and limitations of the model and provide implications for future studies. In addition we give a short exposition on the immunologic properties of LPS, information pathways from the immune system to the brain, and on the cytokine hypothesis of depression.

Systemic inflammation is among the most prominent and most frequently observed responses of the immune system. From everyday challenges like mild infections to severe forms such as chronic inflammatory diseases or sepsis, inflammatory states can develop in many ways over the lifespan. Over the past few decades, it has become clear that inflammatory events can have a strong impact on brain functions. Inflammatory mediators released by activated immune cells induce not only adaptive behavioral responses such as sickness behavior but also can lead to cognitive impairment and may even promote the development of mood disorders. Since most of these aspects cannot be sufficiently modeled in laboratory animals, there is a need for experimental inflammatory models in humans. Intravenous or intramuscular injection of bacterial lipopolysaccharide (LPS, endotoxin) represents a model to induce transient systemic low-grade inflammation in healthy human subjects. During the past two decades, this model has been increasingly used for psychoneuroimmunology (PNI) research. After a brief introduction into sickness behavior and the history of immune-to-brain research, we will summarize work employing this promising model beginning with the first studies on sleep alterations and ending with studies on social behavior using cutting-edge neuroimaging techniques like functional magnetic resonance imaging (fMRI) or positron emission tomography (PET). We will discuss potential difficulties and limitations of the model and provide implications for future studies. In addition we give a short exposition on the immunologic properties of LPS, information pathways from the immune system to the brain, and on the cytokine hypothesis of depression.

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Authors and Affiliations

  1. Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany

    Jan-Sebastian Grigoleit, Harald Engler & Manfred Schedlowski

  2. Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, CA, 92037, USA

    Jan-Sebastian Grigoleit

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  1. Jan-Sebastian Grigoleit
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  3. Manfred Schedlowski
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Correspondence to Manfred Schedlowski .

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  1. University Clinic, Campus Innenstadt Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany

    Norbert Müller

  2. University Clinic, Campus Innenstadt PsychoNeuroImmunology Research Group, Ludwig-Maximilians-University Munich, Munich, Germany

    Aye-Mu Myint

  3. Institute fuer Laboratoriumsmedizin, Klinikum der Universitaet Muenchen, Muenchen, Germany

    Markus J. Schwarz

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Grigoleit, JS., Engler, H., Schedlowski, M. (2015). Experimental Human Endotoxemia, Sickness Behavior, and Neuropsychiatric Diseases. In: Müller, N., Myint, AM., Schwarz, M. (eds) Immunology and Psychiatry. Current Topics in Neurotoxicity, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-319-13602-8_4

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