Cited by 498Cytokine Signaling Pathways and InteractionsNeuroinflammation and Neurodegeneration MechanismsTryptophan and brain disorders

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The role of interleukin-6 signaling in nervous tissue

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Rothaug, Michelle, Becker-Pauly, Christoph, Rose-John, Stefan·2016·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

DOI 10.1016/j.bbamcr.2016.03.018

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Abstract

The cytokine interleukin-6 (IL-6) plays a critical role in the pathogenesis of inflammatory disorders and in the physiological homeostasis of neural tissue. Profound neuropathological changes, such as multiple sclerosis (MS), Parkinson's and Alzheimer's disease are associated with increased IL-6 expression in brain. Increased nocturnal concentrations of serum IL-6 are found in patients with impaired sleep whereas IL-6-deficient mice spend more time in rapid eye movement sleep associated with dreaming. IL-6 is crucial in the differentiation of oligodendrocytes, regeneration of peripheral nerves and acts as a neurotrophic factor. It exerts its cellular effects through two distinct pathways which include the anti-inflammatory pathway involving the membrane-bound IL-6 receptor (IL-6R) expressed on selective cells, including microglia, in a process known as classical signaling that is also critical for bacterial defense. In classical signaling binding of IL-6 to the membrane-bound IL-6R activates the β-receptor glycoprotein 130 (gp130) and subsequent down-stream signaling. The alternative, rather pro-inflammatory pathway, shown to mediate neurodegeneration in mice, termed trans-signaling, depends on a soluble form of the IL-6R that is capable of binding IL-6 to stimulate a response on distal cells that express gp130. A naturally occurring soluble form of gp130 (sgp130) has been identified that can specifically bind and neutralize the IL-6R/IL-6 complex. Thus, trans-signaling is blocked but classical signaling is completely unaffected. A modified, recombinant dimerized version of sgp130 (sgp130Fc) has successfully been used to block inflammatory processes in mice and may also be used in the clarification of IL-6 trans-signaling in neurological diseases.

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Authors: Rothaug, M., Becker-Pauly, C., & Rose-John, S.
Affiliations: Christian-Albrechts-Universität zu Kiel (DE)
Venue: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Publisher: Elsevier BV
Published: 2016-06
Volume: 1863
Issue: 6
Pages: 1218-1227
ISSN: 0167-4889 (ISSN-L)
DOI: 10.1016/j.bbamcr.2016.03.018
OpenAlex: W2308447553
Cited by: 491
References: 170
Citations by year: 2026: 30 · 2025: 51 · 2024: 44 · 2023: 54 · 2022: 89 · 2021: 74 · 2020: 59 · 2019: 37 · 2018: 22 · 2017: 23 · 2016: 8
FWCI: 3.02
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 365 d)
Locations: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft (SFB 654)
Proteolysis as a Regulatory Event in Pathophysiology (SFB 877)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: interleukin-6, IL-6 signaling, neuroinflammation, multiple sclerosis, Parkinson's disease, Alzheimer's disease, sleep, REM sleep, oligodendrocyte differentiation, peripheral nerve regeneration, neurotrophic factors, soluble IL-6 receptor, gp130, trans-signaling, sgp130Fc, neurodegeneration, microglia
MeSH terms: Animals, Central Nervous System, Humans, Models, Biological, Protein Binding, Signal Transduction, Interleukin-6, Neurodegenerative Diseases, Receptors, Interleukin-6, Cytokine Receptor gp130

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The role of interleukin-6 signaling in nervous tissue

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