IL-6 regulation of synaptic function in the CNS

Gruol, Donna L.

doi:10.1016/j.neuropharm.2014.10.023

Cited by 254Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersNeuroscience and Neuropharmacology Research

IL-6 regulation of synaptic function in the CNS

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Gruol, Donna L.·2015·Neuropharmacology

DOI 10.1016/j.neuropharm.2014.10.023PMC PMC4446251

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Abstract

A growing body of evidence supports a role for glial-produced neuroimmune factors, including the cytokine IL-6, in CNS physiology and pathology. CNS expression of IL-6 has been documented in the normal CNS at low levels and at elevated levels in several neurodegenerative or psychiatric disease states as well as in CNS infection and injury. The altered CNS function associated with these conditions raises the possibility that IL-6 has neuronal or synaptic actions. Studies in in vitro and in vivo models confirmed this possibility and showed that IL-6 can regulate a number of important neuronal and synaptic functions including synaptic transmission and synaptic plasticity, an important cellular mechanism of memory and learning. Behavioral studies in animal models provided further evidence of an important role for IL-6 as a regulator of CNS pathways that are critical to cognitive function. This review summarizes studies that have lead to our current state of knowledge. In spite of the progress that has been made, there is a need for a greater understanding of the physiological and pathophysiological actions of IL-6 in the CNS, the mechanisms underlying these actions, conditions that induce production of IL-6 in the CNS and therapeutic strategies that could ameliorate or promote IL-6 actions. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'.

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Stress-related increases in cortisol and pro-inflammatory cytokines affect NMDA receptor function.
“For example, stress-related increases in levels of cortisol and pro-inflammatory cytokines affect NMDA receptor (NMDAR) function (Nair and Bonneau, 2006; Gruol, 2015; Vezzani and Viviani, 2015).”
From Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression (2016) · cites this paper as Gruol, 2015
Section 6.2 (page not available in our copy) reports that chronic IL-6 exposure increased developing neurons’ response to NMDA, supporting the cytokine–NMDAR part of the claim. It does not establish that stress-related increases in cortisol affect NMDAR function, or that the IL-6 effect observed was caused by stress. (LLM, conf=0.86)
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“, sleepdependent memory consolidation), which can be disrupted by abnormal levels of IL-6 in the CNS (Benedict et al., 2009; Dimitrov et al., 2006; Heffner et al., 2012; Hong et al., 2005; Irwin et al., 2004).”
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Chronic interleukin‐6 exposure alters metabotropic glutamate receptor‐activated calcium signalling in cerebellar Purkinje neurons
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Aberrant cytokine gene expression in the hippocampus in murine systemic lupus erythematosus
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“A number of studies have reported elevated levels of IL-6 during central nervous system (CNS) disorders [65], but on the other hand Ma and co-workers [71], demonstrated that IL-6 reduced neuronal cytosolic Ca2+ overload, mitochondrial membrane depolarization, and neuronal induced by NMDA, demonstrating that IL-6 has a…”
Background

Authors: Gruol, D. L.
Affiliations: Scripps Research Institute (US)
Corresponding author: Gruol, Donna L.
ORCID: Gruol, Donna L.
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2015-09
Volume: 96
Issue: Pt A
Pages: 42-54
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/j.neuropharm.2014.10.023
PMC: PMC4446251
OpenAlex: W2016883790
Cited by: 254
References: 180
Citations by year: 2026: 18 · 2025: 27 · 2024: 18 · 2023: 29 · 2022: 26 · 2021: 29 · 2020: 32 · 2019: 28 · 2018: 20 · 2017: 10 · 2016: 13 · 2015: 4
FWCI: 4.67
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: NIH (AA019261, AA07456, MH083723, MH63712, MH62261, MH47680, HD38231, DA10187)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: interleukin-6, synaptic function, neuroimmunology, synaptic transmission, synaptic plasticity, learning and memory, cognitive function, neurodegenerative diseases, mental illness, central nervous system infection, central nervous system injury, neuroinflammation
MeSH terms: Animals, Brain, Brain Diseases, Cognition, Hippocampus, Humans, Learning, Memory, Mice, Transgenic, Synaptic Transmission, Neuroglia, Neuronal Plasticity, Neurons, Synapses, Neuroimmunomodulation, Interleukin-6

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IL-6 regulation of synaptic function in the CNS

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