title: 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'.
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Department of Neuroscience, Milano, Italy. Electronic address: annamaria.vezzani@marionegri.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Vezzani
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, Milano, Italy. Electronic address: barbara.viviani@unimi.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Viviani
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D015398:Signal Transduction; D009435:Synaptic Transmission; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D024642:Potassium Channels, Voltage-Gated; D014409:Tumor Necrosis Factor-alpha; D061566:Voltage-Gated Sodium Channels
keywords: Blood–brain barrier; Channelopathy; Cognition; Epilepsy; Glia; Glutamate and GABA receptors; Innate immunity; Neuroinflammation; Neuropathology; Synaptic transmission