Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability
Abstract
Increasing evidence underlines that prototypical inflammatory cytokines (IL-1β, TNF-α and IL-6) either synthesized in the central (CNS) or peripheral nervous system (PNS) by resident cells, or imported by immune blood cells, are involved in several pathophysiological functions, including an unexpected impact on synaptic transmission and neuronal excitability. This review describes these unconventional neuromodulatory properties of cytokines, that are distinct from their classical action as effector molecules of the immune system. In addition to the role of cytokines in brain physiology, we report evidence that dysregulation of their biosynthesis and cellular release, or alterations in receptor-mediated intracellular pathways in target cells, leads to neuronal cell dysfunction and modifications in neuronal network excitability. As a consequence, targeting of these cytokines, and related signalling molecules, is considered a novel option for the development of therapies in various CNS or PNS disorders associated with an inflammatory component. 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 Vezzani and Viviani, 2015
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“Keywords: computational psychiatry, effective connectivity, dynamic causal modeling, homeostasis, allostasis, predictive coding, active inference, multiple sclerosis”
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- Authors
- Vezzani, A., & Viviani, B.
- Affiliations
- Mario Negri Institute for Pharmacological Research (IT)
- University of Milan (IT)
- Corresponding author
- Vezzani, Annamaria
- Viviani, Barbara
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 96
- Issue
- Pt A
- Pages
- 70-82
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2021163482
- Cited by
- 670
- References
- 14
- Citations by year
- 2026: 59 · 2025: 68 · 2024: 70 · 2023: 50 · 2022: 65 · 2021: 81 · 2020: 62 · 2019: 48 · 2018: 49 · 2017: 56 · 2016: 41 · 2015: 20 · 2012: 1
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondazione Monzino, Epitarget (FP7/2007-2013)
- Ministero della Salute (RF-2009-1506142)
- 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
- inflammatory cytokines, neuromodulation, neuronal excitability, IL-1β, TNF-α, interleukin-6, synaptic transmission, neuroinflammation, cytokine receptors, neuronal network excitability, neuroimmunology, cytokine-targeted therapy
- MeSH terms
- Animals, Humans, Synaptic Transmission, Neuroglia, Neuronal Plasticity, Neurons, Tumor Necrosis Factor-alpha, Calcium Channels, Signal Transduction, Interleukin-6, Cytokines, Inflammation Mediators, Potassium Channels, Voltage-Gated, Interleukin-1beta, Voltage-Gated Sodium Channels
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