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Innate Immune Signaling and Alcoholism

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Neural-Immune Interactions in Brain Function and Alcohol Related Disorders

Abstract

Chronic use of alcohol and other drugs of abuse have been demonstrated to activate the innate immune system of the CNS. This activation, in turn, may lead to progressive changes to neurobiology that underlie loss of behavioral control and increased limbic negative affect common in addiction. Ethanol exerts effects on the systemic adaptive and innate immune systems [1]. Adaptive immunity comprises a class of highly specialized lymphocytic cells that recognize, remember, and target specific pathogens through the production of antibodies. This system is protective in that it maintains an immunological memory of the pathogen in the lymphocytes in preparation for future insults. In contrast, the innate immune system mounts a nonspecific immune response to a pathogen via secretion of cytokines and other chemical messages that activate cells. This chapter will focus on the effects of alcohol on innate immunity because the brain possesses few lymphocytes and, consequently, minimal adaptive immunity. Although beyond the scope of this chapter, it is important to note that ethanol causes the gut to become “leaky” resulting in the release of the endotoxin lipopolysaccharide (LPS). The increased gut permeability to LPS contributes to liver inflammation and secretion of proinflammatory cytokines [e.g., tumor necrosis factor-alpha (TNFα)] into the blood. The blood is then transported into the brain where TNFα and other cytokines are induced causing neuroinflammation that persists long after the resolution of the peripheral inflammatory response [2] (see Fig. 8.1).

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Acknowledgments

The authors wish to acknowledge support from the Bowles Center of Alcohol Studies, School of Medicine, The University of North Carolina at Chapel Hill, the National Institute of Health, and the National Institute on Alcoholism and Alcohol Abuse through AA020023, AA020022, AA019767, AA11605, and AA007573.

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  1. Department of Pharmacology and Psychiatry, The Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, The School of Medicine, CB #7178, 1021 Thurston-Bowles Building, Chapel Hill, NC, 27599-71780, USA

    Ryan P. Vetreno & Fulton T. Crews Ph.D.

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  1. Ryan P. Vetreno
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  2. Fulton T. Crews Ph.D.
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Correspondence to Fulton T. Crews Ph.D. .

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  1. National Institute on Alcohol Abuse and, Division of Neuroscience and Behavior, NIH, Fishers Lane 5635, Bethesda, 20892, Maryland, USA

    Changhai Cui

  2. National Institute on Alcohol Abuse and, Division of Neuroscience and Behavior, NIH, Fishers Lane 5635, Bethesda, 20892, Maryland, USA

    Lindsey Grandison

  3. National Institute on Alcohol Abuse and, Division of Neuroscience and Behavior, NIH, Fishers Lane 5635, Bethesda, 20892, Maryland, USA

    Antonio Noronha

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Vetreno, R.P., Crews, F.T. (2013). Innate Immune Signaling and Alcoholism. In: Cui, C., Grandison, L., Noronha, A. (eds) Neural-Immune Interactions in Brain Function and Alcohol Related Disorders. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4729-0_8

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