Innate immune signaling and alcoholism

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).