Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability

Neuropharmacology. 2015 Sep;96(Pt A):70-82. doi: 10.1016/j.neuropharm.2014.10.027. Epub 2014 Nov 8.


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'.

Keywords: Blood–brain barrier; Channelopathy; Cognition; Epilepsy; Glia; Glutamate and GABA receptors; Innate immunity; Neuroinflammation; Neuropathology; Synaptic transmission.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium Channels / metabolism
  • Cytokines / metabolism*
  • Humans
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Neuroglia / metabolism
  • Neuroglia / physiology*
  • Neuronal Plasticity
  • Neurons / metabolism
  • Neurons / physiology*
  • Potassium Channels, Voltage-Gated / metabolism
  • Signal Transduction
  • Synaptic Transmission*
  • Tumor Necrosis Factor-alpha / metabolism
  • Voltage-Gated Sodium Channels / metabolism


  • Calcium Channels
  • Cytokines
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Potassium Channels, Voltage-Gated
  • Tumor Necrosis Factor-alpha
  • Voltage-Gated Sodium Channels