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Cytokine networks in neuroinflammation

Nature Reviews Immunology volume 17, pages 49–59 (2017)Cite this article

Subjects

Key Points

  • Much of the development and physiology of the central nervous system (CNS) is governed through cytokine networks, which when deregulated contribute to tissue inflammation.

  • CNS inflammation does not require tissue-invasion by blood-borne cells, but can occur as a result of a local tissue response to abnormal changes in the microenvironment.

  • In degenerative diseases such as proteopathies (for example, Alzheimer disease), CNS-resident cells are the predominant producers of pro-inflammatory cytokines.

  • In classical neuroinflammatory diseases, such as multiple sclerosis and encephalitides, pro-inflammatory cytokines are the major payload delivered by tissue-invading leukocytes.

  • In proteopathies and neurodegeneration, the initial tissue response to disturbances in normal homeostasis is primarily beneficial, that is, intended to counteract or repair the imbalance. On the other hand, chronic over-production of cytokines over long periods of time can also render CNS-resident cells dystrophic or even irreversibly 'exhausted', which in turn fuels the degenerative processes.

  • In inflammatory demyelination or encephalitides, tissue invasion by leukocytes is detrimental and cytokines delivered to the CNS fuel the inflammatory cascade and lead to tissue damage.

  • CNS tissue damage is in all likelihood mediated by tissue-invading myeloid cells and not by lymphocytes. Our understanding of the myeloid response to inflammation and deregulated cytokine networks is still in its infancy.

Abstract

Cytokines provide cells with the ability to communicate with one another and orchestrate complex multicellular behaviour. There is an emerging understanding of the role that cytokines play in normal homeostatic tissue function and how dysregulation of these cytokine networks is associated with pathological conditions. The central nervous system (CNS), where few blood-borne immune cells circulate, seems to be particularly vulnerable to dysregulated cytokine networks. In degenerative diseases, such as proteopathies, CNS-resident cells are the predominant producers of pro-inflammatory cytokines. By contrast, in classical neuroinflammatory diseases, such as multiple sclerosis and encephalitides, pro-inflammatory cytokines are mainly produced by tissue-invading leukocytes. Whereas the effect of dysregulated cytokine networks in proteopathies is controversial, cytokines delivered to the CNS by invading immune cells are in general detrimental to the tissue. Here, we summarize recent observations on the impact of dysregulated cytokine networks in neuroinflammation.

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Figure 1: Neurodegeneration versus neuroinflammation.
Figure 2: Cytokine delivery into the inflamed CNS.

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Acknowledgements

This work was supported by grants from the Swiss national science foundation (310030_146130 and 316030_150768 to B.B.), the European Union, FP7 ITN_NeuroKine and the European Union FP7 project TargetBraIn (279017) (B.B.), the University Priority Project Translational Cancer Research (B.B.) and in part by a National Institute of Allergy and Infectious Diseases Grant R37 AI107494-01 (to J.G.).

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  1. Institute of Experimental Immunology, University of Zurich, Zurich, 8057, Switzerland

    Burkhard Becher & Sabine Spath

  2. Department of Immunology, University of Washington, Seattle, 98109-8059, Washington, USA

    Joan Goverman

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  1. Burkhard Becher
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Correspondence to Burkhard Becher.

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Becher, B., Spath, S. & Goverman, J. Cytokine networks in neuroinflammation. Nat Rev Immunol 17, 49–59 (2017). https://doi.org/10.1038/nri.2016.123

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