Ethanol and Cytokines in the Central Nervous System

Marisa Roberto*, Reesha R. Patel, Michal Bajo

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

29 Scopus citations

Abstract

The innate immune system plays a critical role in the ethanol-induced neuroimmune response in the brain. Ethanol initiates the innate immune response via activation of the innate immune receptors Toll-like receptors (TLRs, e.g., TLR4, TLR3, TLR7) and NOD-like receptors (inflammasome NLRs) leading to a release of a plethora of chemokines and cytokines and development of the innate immune response. Cytokines and chemokines can have pro- or anti-inflammatory properties through which they regulate the immune response. In this chapter, we will focus on key cytokines (e.g., IL-1, IL-6, TNF-α) and chemokines (e.g., MCP-1/CCL2) that mediate the ethanol-induced neuroimmune responses. In this regard, we will use IL-1β, as an example cytokine, to discuss the neuromodulatory properties of cytokines on cellular properties and synaptic transmission. We will discuss their involvement through a set of evidence: (1) changes in gene and protein expression following ethanol exposure, (2) association of gene polymorphisms (humans) and alterations in gene expression (animal models) with increased alcohol intake, and (3) modulation of alcohol-related behaviors by transgenic or pharmacological manipulations of chemokine and cytokine systems. Over the last years, our understanding of the molecular mechanisms mediating cytokine- and chemokine-dependent regulation of immune responses has advanced tremendously, and we review evidence pointing to cytokines and chemokines serving as neuromodulators and regulators of neurotransmission.

Original languageEnglish (US)
Title of host publicationHandbook of Experimental Pharmacology
PublisherSpringer New York LLC
Pages397-431
Number of pages35
DOIs
StatePublished - 2018

Publication series

NameHandbook of Experimental Pharmacology
Volume248
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

Keywords

  • Alcohol
  • Inflammatory mediators
  • Neuroimmune system
  • Synaptic transmission

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • Biochemistry

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